由湖南师范大学和中国科学院理论物理研究所共同举办的“第六届海峡两岸生物学启发的理论问题研讨会”于6月25-28日在湖南省张家界召开。本研究室向大会报告了：从衰老生化本质看“上医治未病”的科学道理 的研究成果。 顺便将其他专家的报告也给出如下，以飨同道中人：

从衰老生化本质看“上医治未病”的科学道理

印大中*

湖南师范大学生命科学学院 衰老生化研究室 湖南长沙 410081

^{E-mail: dazhongyin@hotmail.com}

尽管“上医治未病”是中医对待疾病和健康问题的一个突出的思维优势，但解读其中隐含的科学原理却是中西医结合生命科学所面临的极大的难题。本专题以系统生物医学和老年医学的最新研究进展为基础，以（能量）代谢组学和蛋白质表达后在衰老过程中的生化变化规律及其相互作用的专业知识为启迪，将“中医治本”与生命在应激过程中出现的“亚健康”生理生化过程贯通思考，为传统中医体系中诸多“防重于治”的医疗措施和理论提出了现代科学的解释。

第六届海峡两岸生物学启发的理论问题研讨会

会议论文摘要

1．Microbial Structural Genomics: Important Functions Carried Out by Huge Protein Polymers

周三和

中興大學生化研究所

shchou@nchu.edu.tw

Structural genomics is crucial for understanding the intricate interactions among proteins in a whole organism. We have studied the structural genomics of Xanthomonas campestris (Xcc), a gram-negative bacterium that is phytopathogenic to cruciferous plants and causes worldwide agricultural loss. Xcc is the only bacterium known to lack a cAMP signaling system, and uses a cAMP-receptor protein like protein (CLP) system instead. Currently we are working on its flagellar and SOS structural genomics.

In the flagellar system, we have solved the first crystal structure of a hook-capping protein FlgD. The core structure reveals a novel hybrid comprising a tudor-like domain interdigitated with a fibronectin type III domain. In the crystal, the monomers form an annular pentamer of dimers of pseudo five-fold symmetry, due to the different dimer-dimer interactions incorporated. The resulting asymmetrical star-like decamer complex has a outer dimensions of approximately 110 A x 90 A x 65 A, and a shortest diameter of approximately 20 A in the center. The outer dimensions of the atomic Xcc hook-capping FlgD complex turn out to be very similar to those of the Salmonella filament cap complex observed by electron microscopy.

SOS has been the most intensively studied system induced under DNA damage, and is characterized by the induction of more than 20 genes, which are under the control of LexA. In response to DNA damage, RecA is activated to induce the auto-cleavage of LexA, resulting in de-repression of genes in the SOS regulon. The recX gene is co-transcribed with recA and its product is suggested to regulate RecA function by directly interacting with RecA protein. We have solved the first RecX structure to a resolution of 1.6 A. It is a curved structure comprising three tandem repeats R1, R2 and R3 of three-helix bundles. Model studies indicate RecX can fit into the helical groove of the RecA filament very well, similar to that reported for the cryoEM image of the RecA/RecX/ATP/ssDNA complex.

2．Can mathematics help curing cardiac arrhythmias?

洪子倫

逢甲大學應用數學系

tlhorng@math.fcu.edu.tw

Ventricular Tachycardia (VT) and Ventricular Fibrillation (VF) are serious symptoms of Arrhythmias with VF especially being fatal. They correspond to spiral wave and spiral wave break-up (multiple spiral waves) of action potential wave respectively. Mechanisms of forming spiral wave and spiral wave break-up and elimination of them are currently a major research subject of cardiac electrophysiology in both medical experiments and mathematical modeling. In the current talk, I will talk about the formation of spiral waves and its break-up due to instability; how the spiral waves interact with heterogeneous ventricular structure like papillary muscle; how to eliminate spiral waves via wavelength theory based on the restitution property of cardiac myocyte. 2D simulation of mono-domain equation associated with a reduced ionic channel current model, Aliev-Panfilov model, has been computed and the results will be demonstrated here to show the effectiveness of wavelength restitution theory.

3．基因體中的反對稱及全基因體的反對稱複製

康星源

中央大學

kensinro@hotmail.com

片段複製長久以來被當作基因體成長及演化的重要機制，最近確實了全基因體複製的確發生在酵母菌及一些硬骨魚種類當中。在這裡，我們提供了證據證明全基因體反對稱複製非常可能發生在至少一半的真細菌當中，更甚至絕大部份的染色體當中。我們研究了現有資料庫提供的染色體的反對稱並從中得到我們的證據。發現了絕大部份的染色體都擁有全域的反對稱，但在局部上的反對稱卻有幾種不同的樣式。這些樣式為反對稱片段複製發生在基因體中的一致論述提供了線索。

4．Synchronizations in Growing Cardiac cultured cells

黎璧賢

中央大學物理系及生物物理所

W. Chen, S. C. Cheng, E. Avalos, O. Drugova, G. Osipov, Pik-Yin Lai and C. K. Chan

Synchronization of heterogeneous systems consisted of oscillatory and passive elements are studied in cardiac myocytes (CM)/fibroblasts (FB) co-cultures. It is found that beating clusters of CM surrounded by FB will be formed. The beatings of the CM clusters are not correlated at early times but get synchronized as the cultures mature. This synchronization can be understood by a Kuramoto model with a time increasing coupling strength. Our findings suggest that this growth of the coupling strength is due to the proliferations of the FB and the overall wave dynamics of the system is controlled by the passive FB in the system..

5．Effect of Density on the aggregation of Slime mould

陳志強

中央研究院物理所

ckchan@gate.sinica.edu.tw

6．System-wide coordination for tunable scale-free networks

罗煜聘

国家理论科学中心物理组

yupinluo@gmail.com

Many natural and social systems display global organization and coordination without centralized control. Here we investigate a density-classification task as a model system for coordination and information processing in decentralized systems [PNAS 101,12085 (2004)]. We show that the efficiency of system coordination influenced by degree distribution and clustering coefficient in scale-free network. The scale-free networks are constructed based on the Barabasi-Albert (BA) construction algorithm. By modifying the preferential attachment step of the BA construction algorithm [Physica A 382,731 (2007) ], we can specify the power of degree distribution and the clustering coefficient.

7．Guiding Proteins through Folding Pathways by Dynamical Contact Map

牟中瑜, 陳南佑

清華大學物理系, 新竹

mou@phys.nthu.edu.tw

An optimization method based on dynamical configuration of contacts is proposed to guide proteins fold. The method is combined with an off-lattice model with realistic potentials. When applying to analyze the folding of two wild-type proteins, protein G and protein L, it yields correct native structures and retrieves major dynamical pathways without resorting to the knowledge of native structures or the complete free energy landscape. It is shown that the statistical potentials associated with the Miyazawa-Jernigan matrix play the dominant role in guiding proteins through the correct folding pathway.

8．Identifying discriminative amino acids within the Hemagglutinin of human influenza A H5N1 virus using a decision tree

吳立青

中央大學系統生物與生物資訊研究所

richard@mail.sybbi.ncu.edu.tw

Recently, the H5N1 virus has had an increasingly important impact on human life. This is because more and more people are becoming infected with this virus and the possibility of a serious pandemic with human to human transmission is looming. This might occur if the genome of this influenza virus mutates either by antigenic drift or antigenic shift, especially if there is mutation of the hemagglutinin (HA) glycoprotein. Hemagglutinin is the surface glycoprotein, and it binds to the sialic acid of the host cell surface receptor. Thus, the linkage of HA and sialic acid are central to whether an influenza virus is able to infect humans. In this study, we selected 497 HA protein sequences from the NCBI Influenza Resource database and used a decision tree method to identify discriminative amino acids in the HA protein sequences that may possibly influence the binding of HA to sialic acid. Four such amino acid positions at 54, 55, 241 and 281 were identified and it seems likely that these may play an important role in infection by H5N1 influenza virus.

9．分析原核生物基因體複製起點與終點的反向對偶對稱現象

許梓亭

中央大學生物資訊與系統生物研究所

lecia.hsu@gmail.com

全基因體的複製現象已經被證實曾經發生在酵母菌的染色體上，藉著廣泛地分析 157 個原核生物，包含 18 個古細菌和 139 個細菌，我們發現一個相當有趣的現象，在這些原核生物的複製起點與終點，有相當顯著的反向對偶對稱現象；這樣子的現象和曾經發生在酵母菌並且被證實的全基因體複製現象又不盡相同，目前也還沒有相關文獻提出一個合理的解釋和證據，我們認為這種現象可能是因為這些原核生物曾經發生全基因體的反向對偶複製，而這種複製就發生在複製起點與終點附近；我們將對這項假設進行驗證並且提出證據，除了做基礎的 DNA 序列分析與計算來佐證，還利用同源基因的分布來觀察是否得已證實這項假設；除此之外，藉由各種原核生物基因體發生反向對偶對稱現象的差異性，可以把這些原核生物分成四種類型生物；另外我們也可以將反向對偶對稱現象當作一項特徵，來進行基因體複製起點與終點的位置預測。

10．Ni-DNA: a Semiconducting polymer

張家靖

交通大學生物科技學系/中央研究院物理所

ccchang01@faculty.nctu.edu.tw

DNA is a one-dimensional nanowire in nature, and it may not be used in nanodevices due to its low conductivity. In order to improve the electron transport properties of DNA, divalent Ni^2＋ metal ions are incorporated into the base pairs of DNA at pH ≧ 8.5 and Ni-DNA is formed. Conducting scanning probe microscopy (SPM) analysis reveals that the Schottky barrier of Ni-DNA reduces to 2 eV. Meanwhile, electrochemical analysis by cyclic voltammetry and AC impedance shows that the resistance of Ni-DNA is lower than that of native DNA by a factor of approximately 20 fold. UV spectroscopy and DNA base pair mismatch analyses of Ni ions doping DNA show that electrons hoping through the stacking of DNA base pairs are the mechanism which makes DNA turning into semiconductor like polymer. This biomaterial is a good one-dimensional conducting polymer for usage in nanodevices.

11．具相關性資料之有母數強韌分析法

鄒宗山

中央大學統計研究所系統生物與生物資訊研究所

tsou@mx.stat.ncu.edu.tw

具相關性(含縱貫性(longitudinal))資料分析之困難處主要在於缺乏合適的聯合機

率分配函數來做為母體分配之假設，因此統計推論較為困難!

在此我們以縱貫性個數資料(count data)為例，介紹一個有母數(parametric)

的強韌方法!在大樣本的情況下，不論資料真正的分配為何，這個有母數的強韌

方法提供參數正確的統計推論!我們並以台灣之健保資料為例，介紹此強韌有母

數方法的簡單應用。而這裡也展示此強韌有母數方法較廣義估計方程式方法好。

12．Sequence-Dependent Effects on the Properties of Semiflexible Biopolymers
Zicong Zhou (周子聰)

台灣淡江大學物理系

zzhou@mail.tku.edu.tw

Using path integral technique, we show exactly that for a semiflexible biopolymer in constant extension ensemble, no matter how long the polymer and how large the external force may be, the effects of short range correlations in the sequence-dependent spontaneous curvatures and torsions can be incorporated into a model with well-defined mean spontaneous curvature and torsion as well as a renormalized persistence length. In contrast, the effects of sequence-dependent persistence lengths are complex. For a long biopolymer with large mean persistence length, the sequence-dependent persistence lengths can be replaced by its mean. However, for a short biopolymer or for a biopolymer with small persistence lengths, inhomogeneity in persistence lengths tends to make physical observables very sensitive to details and therefore less predictable.

13．Effect of Gaussian Noises on Genetic Regulatory Networks

黃敏章

中原大學物理系，中壢市

ming@phys.cycu.edu.tw

Stochastic fluctuations are essential for genetic regulatory networks. Based on Ito calculus, we derive the general expressions for the variances and covariances of molecular concentrations caused by Gaussian white and colored noises. Moreover, the general formulae are applied to specific systems, auto-regulatory networks and genetic toggle switches. In particular, the effect of correlation time of Gaussian noise on fluctuation for the systems is analyzed.

14．Multiscale Biomolecular Simulations and Drug Design

林榮信

中央研究院應用科學研究中心

jhlin@gate.sinica.edu.tw

With the advent of novel computational algorithms, along with the ever-increasing computing and networking speed, molecular simulations both at the length scale and time scale of biological relevance have now become reality. In this seminar I will talk about molecular modeling and simulations of some biological systems, including the well-known drug targets G-protein coupled receptors, molecular motor F₀F₁ ATP synthases, and a membrane targeting signaling protein, protein kinase C (PKC), which are of biological and pharmacological significance. Simulations with particle models, either at atomic level or coarse grained level, and with continuum models like Poisson-Boltzmann theory, were employed to address various issues of these systems.

15．Unfolding and refolding of proteins

胡進錕

中央研究院物理所

huck@phys.sinica.edu.tw

In this talk, I briefly review our numerical approach to unfolding of proteins by mechanical force or thermal activation and refolding of protein when the applied force or temperature is reduced. The problems under discussion include: 1. Multiple stepwise refolding of immunoglobulin domain I27 upon force quench [Proc. Natl. Acad. Sci. USA 103, 93 (2006)], 2. Refolding upon force quench and pathways of mechanical and thermal unfolding of ubiquitin, [Biophysical J. 92, 547(2007)], .3. New force replica exchange method and protein folding pathways probed by force-clamp technique [ J. Chem. Phys 128, 045103 (2008)].

16．The identification of microRNA targets in mammalian genomes

黃憲達

交通大學生物資訊所

bryan@mail.nctu.edu.tw

MicroRNAs (miRNAs) are small noncoding RNA molecules, which can negatively regulate gene expression and thus control numerous cellular mechanisms. This work develops a resource, miRNAMap 2.0, for collecting experimentally verified microRNAs and experimentally verified miRNA target genes in human, mouse, rat, and other metazoan genomes. Three computational tools, miRanda, RNAhybrid and TargetScan, were employed to identify miRNA targets in 3’-UTR of genes as well as the known miRNA targets. Various criteria for filtering the putative miRNA targets are applied to reduce the false positive prediction rate of miRNA target sites. Additionally, miRNA expression profiles can provide valuable clues on the characteristics of miRNAs, including tissue specificity and differential expression in cancer/normal cell. Therefore, Q-PCR experiments were performed to monitor the expression profiles of 224 human miRNAs in 18 major normal tissues in human. The negative correlation between the miRNA expression profile and the expression profiles of its target genes typically helps to elucidate the regulatory functions of the miRNA. The interface is also redesigned and enhanced. The resource is now available at http://miRNAMap.mbc.nctu.edu.tw/.

17．Global and Local Inverse Symmetry in Complete Genomes

李弘謙

中央大學生物資訊與系統生物研究所

hclee@sansan.phy.ncu.edu.tw

18．利用知識進化演算法，研究蛋白質模型的能量曲面

鄒忠毅

中國文化大學物理學系

cichou@faculty.pccu.edu.tw

19．growth models for genomes

范文郎

中央大學物理所

alangfan@gmail.com

基因體的研究已有大量的資料，也做了不同方面的探討。各物種的基因體大小不同，鹼基含量的差異也很大。然而，絕大部份的物種都擁有普適性質，例如有效長度、長程關連、對稱性...。根據這些普適性質，我們建立一個盡可能符合真實基因體特性的模型。藉由模擬基因體可能的成長機制，提供了一個研究物種基因體演化過程的方法。

20．Multiscale analysis of genome-wide DNA methylation profiles

王孫崇

中央大學生物資訊與系統生物研究所

scwang@phys.sinica.edu.tw

21．Genetic Switch in Periodically Changing Environments

曾文哲

淡江大學物理系

wjtzeng@mail.tku.edu.tw

We take an extensive analysis about how the cell population evolves in a periodically switching environment either with symmetrical time-span or asymmetrical time-span.  A complete picture of the phase diagrams for both cases is obtained. Furthermore, we find that the systems with time-dependent cellular transitions all collapse to the same set of dynamical equations with the modified parameters. Furthermore, we also explain in detail how the fitness problem bears much resemblance to the phenomenon, stochastic resonance, in physical sciences.

22．3D-BLAST: Protein Structure Database Search and Evolutionary Classification.

楊進木

交通大學生物資訊研究所

moon@faculty.nctu.edu.tw

23．对运动方向进行分类识别或真实估计的神经动力学机制

刘锋

南京大学物理系

fliu@nju.edu.cn

近年来，人们结合神经心理学和神经生理学的方法，研究大脑对运动方向进行选择判断的神经机制。这里，我们通过计算机仿真，分别在神经网络和神经回路的水平上研究抉择过程的神经计算原理。在回返性神经回路中，如果兴奋性突触连接主要为NMDA受体所介导和存在强的抑制性突触连接，神经网络能通过对感觉信号的时间整合和竞争获胜机制，实现对运动方向的判断。计算机仿真结果与实验数据吻合，阐明了抉择过程可能的神经元和突触动力学机制，并提出可供实验检测的理论预言。模型提出的理论框架可用来研究更复杂的认知过程。

24．生物网络的可设计性

王骏

南京大学物理系

wangj@nju.edu.cn

自然界中多种多样的生物网络结构常常表现出相似的动力学特征。这些普遍存在的动力学特点是自然选择的结果还是有着其他物理的来源？我们针对简化的Boolean网络模型，给出了一种网络可设计性的几何描述，并结合几何描述，探讨了高可设计性与网络动力学特征的关系，为理解生物网络的动力学特征提供了一个可能的思路。

25．Study on the Binding Mode of HIV-1 Integrase with Viral DNA by Molecular Modeling

Wei-Zu Chen（陈慰祖）, Jian-Ping Hu, Guo-Tao Ke, and Cun-Xin Wang

北京工业大学生命科学与生物工程学院

The prevalence of AIDS dramatically threatens human life health, which makes the drug design against AIDS as a hot field. Human immunodeficiency virus (HIV) integrase (IN) is an important target for designing and developing the novel anti-HIV drugs. In the life cycle of HIV, IN aids the integration of viral DNA into the host chromosome. Thus, the study of the effective recognition mechanism of IN with viral DNA is very important for designing the anti-HIV drug against IN.

In order to explore the interactions and binding mode of HIV IN with viral DNA, the specific binding mode between IN dimer and its substrate 27 bp segments of viral DNA was investigated via the molecular docking method. The results show that the key residues for IN dimer binding with viral DNA are Lys14, Arg20, Lys156, Lys159, Lys160, Lys186, Lys188, Arg199 residues in the chain B and Lys219, Trp243, Lys244, Arg262, Arg263 residues in the chain A. The explanation for the minimum length of 15 bp viral DNA to activate IN was given based on the docked complex structure. Through the binding energy analysis, it is found that non-polar interactions are the principal factor favoring the binding of IN with DNA; whereas, the stable association of viral DNA with the key residues are mainly driven by polar interactions.

Based on the binding mode obtained by molecular docking, the change of motive mode, correlative movement and viral DNA conformational change were explored and analyzed with molecular dynamics (MD) simulation and statistical methods. Then, the solvent effect during the association of IN dimer with viral DNA is analyzed briefly. The result shows that viral DNA can be divided into five regions (i.e. non-binding region, high-affinity region 1, weak-affinity region, high-affinity region 2 and reaction region) according to the binding activity. When viral DNA is associated with IN dimer, some significant changes occur in both the motive mode and the cooperative movement for each system. It is found that the big conformational changes appear for the bases in the binding region other than the non-binding region for viral DNA bound with IN. The obvious deviation from standard B-DNA in the viral DNA main chain of the complex and the broading of the minor groove in the binding site are both the fundamentals for the recognition basis of viral DNA with IN dimer. Through analyzing the hydrogen bonds formed by water in the interface between IN dimer and viral DNA, it is found that water molecules play an important role in the recognition between IN and viral DNA.

Since HIV-1 IN expressed in human cells indeed presents as a stable tetramer, the binding mode of IN tetramer with viral DNA and the mechanism of the integration process were also studied in this work. The association of the IN tetramer with eight different length segments of viral end DNA were investigated by using DOT package. The DNA binding regions of IN tetramer and the influence of the length of viral DNA to the association were explored based on the simulation data. The results indicate that there are three DNA binding regions of IN tetramer for viral DNA. It is found that two regions are the viral DNA binding regions and the rest one is the host DNA binding region. All the above simulation results agree well with the experimental data and provide a more complete structural basis for revealing integration mechanism and for application in anti-HIV drug design.

26．REMAS: a new regression model to identify alternative splicing from Affymetrix exon array data

邓明华

北京大学数学科学学院

dengmh@pku.edu.cn

Alternative splicing contributes a lot to the regulation of gene expression and diversity of proteins and thus is highly relevant to diseases and therapies. Understanding this process will be helpful for drug discoveries and diagnostics efforts. Exon array, a novel exon-centric microarray platform, enables a promising level of analysis on alternative splicing by profiling the expression of all known and predicted exons. The method for mining information that contributes to the prediction of alternative splicing based on the exon array data has raised lots of attention. However, more powerful method for revealing alternative splicing is still necessary because of the complexity of exon array data.

In this study, we consider the problem of identifying alternative splicing events in the framework of variable selection. Using reasonably defined variables, we scale the features of alternatively spliced exons. Regarding the possible transcriptional influence from gene level, we introduce a hierarchical model to represent such characteristics. The lasso type penalties are adopted in the implement of calculation in spite of huge variable size. Then an iterative two-step algorithm is developed to select genes undergoing alternative splicing regulation as well as specific alternatively spliced exons. To avoid negative effect of small sample size, we utilize an iterative procedure to rank the genes for determining the relationships between alternative splicing events and biological features. Both simulation and real data analysis show that our methods named REMAS (Regression Method for Alternative Splicing detection) can identify potential alternative splicing events in an efficient way.

27．人工驯化与选择对作物基因组的影响

樊龙江

浙江大学

fanlj@zju.edu.cn

受人工驯化与选择（育种）的基因位点是与作物形成和重要农艺性质紧密相关的重要位点。以中国糯玉米蜡质基因位点和其他与淀粉代谢途径相关基因位点为例，通过分子群体遗传学等途径，分析人工驯化与选择对作物基因组的影响。提出并讨论检测作物基因组中受人工驯化与选择位点的理论与方法问题。

28．生命之树的原核生物枝

郝柏林

复旦大学物理系

Hao@mail.itp.ac.cn

29．蛋白质和多肽纤维化研究

来鲁华

北京大学化学与分子工程学院/理论生物学中心

lhlai@pku.edu.cn

蛋白质和多肽在特定条件下容易聚集形成纤维，在人体内会导致多种疾病，如老年痴呆、帕金森病等。虽然很多蛋白质在一定条件下都可以被诱导出纤维结构，但不同序列的成纤维性有很大差异。本报告将介绍我们对于多肽聚集早期过程的研究，所发展的多肽成纤维性预测方法，以及根据FRET实验信号进行纤维结构类型判断的方法。

30．Structure Prediction of Protein-protein Complex via Molecular Docking

Chun-Hua L（李春华）, Shan Chang, Xin-Qi Gong, Wei-Zu Chen, and Cun-Xin Wang

北京工业大学生命科学与生物工程学院

Protein-protein docking is usually exploited with a two-step strategy, i.e., conformational sampling and decoy scoring. In our work, we proposed a new filter enhanced sampling scheme and added it into the RosettaDock algorithm to improve the conformational sampling efficiency. The filter term is based on the statistical result that backbone hydrogen bonds in the native protein structures are wrapped by more than nine hydrophobic groups to shield them from attacks of water molecules. A combinatorial scoring function, ComScore, specially designed for the other-type protein–protein complexes was also adopted to select the near native docked modes. ComScore was composed of the atomic contact energy, van der Waals, and electrostatic interaction energies, and the weight of each item was fit through the multiple linear regression approach. To analyze our docking results, the filter enhanced sampling scheme was applied to targets T12, T20, and T21 after the CAPRI blind test, and improvements were obtained. The ligand least root mean square deviations (L_rmsds) were reduced and the hit numbers were increased. ComScore was used in the scoring test for CAPRI rounds 9–12 with good success in rounds 9 and 11.

Besides, we proposed a network-based scoring method. Protein-protein complex, composed of hydrophobic and hydrophilic residues, can be divided into hydrophobic and hydrophilic amino acid network structures, respectively. Through analyzing these two different types of networks, we find that they are of small-world properties. Due to the characteristic complementarity of the complex interfaces, protein-protein docking can be viewed as a particular network rewiring; the networks of correctly docked complex conformations have much more increase of the degree values and decay of the clustering coefficients than those of the incorrect ones. Two scoring terms based on the network parameters are proposed, in which the geometric complementarity, hydrophobic-hydrophobic and polar-polar interactions are taken into account. Compared with a two-term energy function, a new simple scoring function HPNet which includes the two network-based scoring terms shows advantages in two aspects, not relying on energy considerations and better discrimination. Furthermore, combing the network-based scoring terms with some other energy terms, a new multi-term scoring function HPNet-combine can also make some improvements to the scoring function of RosettaDock.

31．Real-time observation of E. coli UvrD helicase reveals its unwinding mechanism

李明

中科院物理研究所

mingli@aphy.iphy.ac.cn

Helicases unwind double stranded nucleic acids in nucleoside triphosphate-dependent reactions. Escherichia coli UvrD is a nonring-shaped model helicase, displaying a 3′ to 5′ polarity in DNA unwinding. Using a transverse magnetic tweezer and a DNA hairpin, we measured the unwinding kinetics of UvrD at various DNA-destabilizing forces. We observed features that were not seen in previous single molecule and bulk assays. The patterns of unwinding bursts and the distribution of off-times reveal that a dimer is required to initiate unwinding. Two subunits of the dimer coordinate to unwind DNA processively. The two subunits of the dimers can jointly switch strands and translocate backwards on the other strand to allow slow (~40 bp/s) rewinding, or unbind simultaneously to allow quick rehybridization. Partial dissociation of the dimer results in pauses in the midst of unwinding, or increases the translocation rate (from ~40 to ~150 nt/s) in the midst of rewinding. Moreover, the unwinding rate was surprisingly found to decrease from ~60 to ~10 bp/s when the force is increased from 0 to 12 pN. The results lead to a strained-inchworm mechanism in which a conformational change that bends and tenses the ssDNA is required to activate the dimmer.

32．炎黄一号：第一个黄种人个人基因组

李松岗

北京大学生命科学学院

lsg@pku.edu.cn

33．机械操作Protein L单分子

刘如川

新加坡国立大学

phylr@nus.edu.sg

迄今为止, 重组细胞蛋白质分子的单分子操作基本上都是用原子力显微镜进行的。由于这些蛋白质的短小，用其它技术对它们进行单分子操作仍然是个不小的挑战。这里，我们展示一个新颖的组合技术，即用电磁镊子和渐衰场纳米测量计的结合，可以容易地捕捉到Protein L八聚体的力迫伸展和折叠过程。用这个新技术，我们成功的观测了单个多聚蛋白质的多次伸展和折叠循环，观测时间长达1小时以上，施加在蛋白质分子上的力在7到15皮牛顿之间。虽然原子力显微镜和新技术所施加的力在不同的区间，但两者测量伸展步长和伸展速率得到非常吻合的结果。除子观测到阶梯式伸展的速率和拉伸力大小的指数性关系，我们还用新技术观测到了从未在高拉伸力时观查到的双稳态构型动态转换。我们的实验证明这是一条实现长期机械操作重组细胞蛋白质分子的新的有效途径。

34．Outline and ultimate limit of protein evolution

刘鑫

中科院力学所

liuxin@lnm.imech.ac.cn

Here, by a revealment of dominant factors, we attempt to present some outlines of protein evolution to readers. These factors are revealed by top eigenvectors in the spectrums of eigenvalue decomposition analysis. To reduce the bias induced by closely related sequences in the database, we introduce a parameter, sequence identity by which proteins with sequence identity below certain level are involved in analysis. It is found that, with drop of sequence identity level, residue feature mainly conserved in mutation changes from hydrophobicity to volume. The transition point is at sequence identity ~ 45%. As residue hydrophobicity no longer governs residue substitution, it is a doubt whether importance of hydrophobic interaction declines in conserving the family representative properties among remote homologues. So, we also investigate the contribution of hydrophobic interaction in near and remote homologues. In aligned homologues, hydrophobic interaction systems inbuilt in these proteins are aligned too; and can be deemed to be similar and substitutable with each other. With a comparison of aligned hydrophobic interaction systems, we can catch the representative character of hydrophobic interaction for the corresponding protein family. Here top weighted feature in the substitution of hydrophobic interaction systems is revealed as a function of sequence identity. It is found that a shift happens to the type of physical quantity which governs the substitution of hydrophobic interaction. The number of hydrophobic residue is the dominantly unchangeable part in aligned hydrophobic interactions as sequence identity >30%. Below this point, state of internal hydrophobic force which characterizes the residue-residue pairwise interaction is primarily conserved. With view of this shift, intrinsic requirement of protein evolution is sought in the discussion section. The major conclusions are:  1.  For remote homologues, hydrophobic interaction is still vital in conserving family representative properties, but changes its aspect of emphasis, from conservation of the number of hydrophobic residue to the preservation of family specific hydrophobic force network.  2.  Intramolecular hydrophobic force network has a crucial contribution to the representative hydrophobic interaction of a protein family, meets the intrinsic requirement of protein evolution, and help the conservation of family representative biological properties significantly.

35．从局部随机到整体周期的细胞内钙离子信号

帅建伟

厦门大学 物理系

jianweishuai@xmu.edu.cn

钙离子是细胞内最广泛且又最重要的第二信使。自上世纪90年代以来，细胞内各种局部钙离子信号的相继发现，包括钙烟(puff),钙火花(spark)等，揭示了细胞钙信号传导的局部随机和整体周期的二极特征：纳米微米尺度上微秒量级的随机钙信号事件耦合叠加成宏观尺度上连续的周期性全细胞钙信号。本报告将主要介绍近些年来对细胞内质网释放的多尺度多层次的钙离子信号的实验与模型研究的进展，对钙信号“局部随机-整体周期”的研究可望进一步揭示细胞内信号的简单性与复杂性，随机性与周期性的统一。

36．Protein Unfolding Behavior Studied by Elastic Network Model

Ji-Guo Su(苏计国), Chun-Hua Li, Wei-Zu Chen, and Cun-Xin Wang

北京工业大学 生命科学与生物工程学院

Experimental and theoretical studies have showed that the native-state topology conceals a wealth of information about protein folding/unfolding. In the present study, a method based on the Gaussian network model (GNM) is developed to study some properties of protein unfolding and explore the role of topology in protein unfolding process. The Gaussian network model has been successful in predicting atomic fluctuations around an energy minimum. However, in the Gaussian network model, the normal mode description is linear and cannot be accurate in studying protein folding/unfolding, which has many local minima in the energy landscape. In order to describe the nonlinearity of the conformational changes during protein unfolding, a method based on the iterative use of normal mode calculation is proposed. The protein unfolding process is mimicked through breaking the native contacts between the residues one by one according to the fluctuations of the distance between them. With this approach, the unfolding processes of two proteins, CI2 and barnase, are simulated. It is found that the sequence of protein unfolding events revealed by this method is consistent with that obtained from thermal unfolding by molecular dynamics (MD) and Monte Carlo (MC) simulations. The results indicate that this method is effective in studying protein unfolding. In this method, only the native contacts are considered, which implies that the native topology may play an important role in the protein unfolding process. The simulation results also show that the unfolding pathway is robust against the introduction of some noise, or stochastic characters. Furthermore, several conformations selected from the unfolding process are studied to show that the denatured state does not behave as a random coil, but seems to have highly cooperative motions, which may help and promote the polypeptide chain to fold into the native state correctly and speedily.

Folding core formation is considered to be a key event of protein folding. However, both experiments and simulations have found that it is a challenging task to identify which residues form the folding core. The protein folding core is the subset of the protein’s structure which is formed early during protein folding and broken later during protein unfolding. In this work, the above mentioned method is adopted to simulate the protein unfolding process and the persistent contacts during unfolding are identified. The secondary structures that formed the persistent contacts are considered to be the folding cores. The unfolding processes and folding cores of 20 proteins are studied. It is found that the folding cores identified by this method are consistent with those obtained by Hydrogen exchange experiments. The results imply that our method is efficient to identify protein folding core from its native structures.

37．Inferring functional linkage between proteins from evolutionary scenario.

孙之荣

清华大学生物系，北京

Identifying protein interactions and further generating a network of biological significance is crucial for our understanding many cellular processes. Booming of complete genome sequence data enables us to develop “in silico” methods to predict protein-protein interactions based on genomic information. The phylogenetic profile method is one of such approaches. The concept behind it is that functional related proteins bear a similar evolutionary pressure which results in their similar phylogenetic profiles. Here we introduced a new method for inferring functional linkage between proteins from their evolutionary scenarios. Evolutionary Scenario here refers to a series of evolutionary events in speciation，which can be reconstructed given a phylogenetic profile and a species tree. Existence of a co-related evolutionary pressure on two given proteins then can be detected by comparing their evolutionary scenarios, which is a direct indicator of their functional linkage. The traditional phylogenetic profile method and our method are both implemented for predicting function linkages in the same dataset and our method is proved to have a better performance. In addition, predicted results of two methods are found to be fairly different, which provides a possibility to unit them to reach a better performance. The evolutionary scenario method is used for inferring functional linkages in 67 species and totally 32,425 linkages are predicted. We examine our prediction for budding yeast and find that most of predicted linkages are also supported by other evidences.

Keywords: Interaction; Evolutionary scenario; Phylogenetic profile; Co-occurrence; Evolutionary events

38．Organization and simplification of metabolic networks

汤雷翰

香港浸会大学

lhtang@hkbu.edu.hk

Through evolution living organisms have developed an elaborate network of enzyme-facilitated reactions and transport to process and cycle biochemical compounds for cell growth. To facilitate quantitative analysis of biosynthesis and integration of various types of experimental data on the metabolic flow and regulation, we have developed a systematic scheme to simplify the network based on relevant biochemical knowledge. The basic ideas of the simplification are introduced.

39．Concise theory of chiral lipid membranes

涂展春

北京师范大学物理系

tuzc@bnu.edu.cn

A theory of chiral lipid membranes is proposed on the basis of a concise free energy density which includes the contributions of the bending and the surface tension of membranes, as well as the chirality and orientational variation of tilting molecules. This theory is consistent with the previous experiments [Science 264, 945 (1994); Langmuir 14, 3493 (1998); Proc. Natl. Acad. Sci. USA 102, 7438 (2005)] on self-assembledchiral lipid membranes of DC_8,9PC. The pitch angles of helical ripples are theoretically estimated to be about 0º and 35 º, which are close to the most frequent values 5 º and 28 º observed in the experiment [Langmuir 22, 1973 (2006)]. Additionally, the present theory can explain twisted ribbons of achiral cationic amphiphiles interacting with chiral tartrate counterions. The ratio between the width and pitch of twisted ribbons is predicted to be proportional to the relative concentration difference of left- and right-handed enantiomers, which is in good agreement with the experiment [Nature \textbf{399}, 566 (1999)].

40．Study on the Release of B₁₂ form BtuF with Steered Molecular Dynamics Simulation

Cun-Xin Wang（王存新）, Ming Liu, Ting-Guang Sun, Wei-Zu Chen

北京工业大学 生命科学与生物工程学院

cxwang@bjut.edu.cn

BtuF is a periplasmic binding protein (PBP) that binds vitamin B₁₂ and delivers it to the periplasmic surface of BtuCD. PBP generally exhibits considerable conformational changes during ligand binding process. However, BtuF was found to be a closed structure for both monomer and complex structure with vitamin B₁₂ by X-ray experiment. In this work, the constant-velocity Steered Molecular Dynamics (cv-SMD) simulations were performed to understand the release process of B₁₂ form BtuF.

The complex structure of BtuF and B₁₂ was taken from the crystal structure (PDB entry: 1N4A), including 4008 solute atoms, 9503 water molecules, 9 ions (32526 atoms in total). In the cv-SMD procedure, a virtual spring was attached to the B₁₂ center of mass and was pulled along the minus z-axis with the constant velocity of 5×10^-4 nm/ps. The force constant of the virtual spring is 3500 pN/nm. The cv-SMD simulations were repeated four times with the same initial conditions for calculating the potential of mean force (PMF) employing Jarzynski’s equality. In every cv-SMD simulation, C_α atoms in the interconnection domain of BtuF were constrained (k = 5000 pN/nm) to prevent unexpected deformations. The B₁₂ molecule was slowly pulled out of the binding site along the minus z-axis for d = 1.8 nm (displacement). The simulation time of every cv-SMD simulation is 3.6 ns.

According to cv-SMD simulation data, a potential of mean force was calculated along the vitamin B₁₂ release pathway. The free energy change for B₁₂ unbinding is 113 kJ.mol^-1. This large free energy differences of the B₁₂ release process indicate that the affinity between BtuF and B₁₂ is very strong. From the principal component analysis for the complex of BtuF and B₁₂, it is found that shows clear opening-closing and twisting motion tendencies. These motion tendencies may facilitate the unbinding of B₁₂ from the binding pocket. The intrinsic flexibility of BtuF was also analyzed. It is found that Trp44-Gin45 pair located at the mouth of the B₁₂ binding pocket acts as a gate in the B₁₂ binding and unbinding process. All above results are helpful for us to understand the release process of B₁₂ form BtuF.

41．利用布朗动力学研究组蛋白与DNA的相互作用

王鹏业

中国科学院物理研究所，软物质物理实验室

pywang@aphy.iphy.ac.cn

利用布朗动力学模拟方法研究了核小体的形成动力学，提出了组蛋白八聚体旋转模型来解释DNA与组蛋白八聚体的作用过程。组成核小体的DNA在受到拉伸力时，组蛋白可被从核小体中剥离下来。我们模拟了这一拉伸的过程，得到了剥离过程的详细图像，给出了拉伸力与拉伸长度的关系和拉伸台阶。根据模拟结果提出了组蛋白的剥离模型。

通过可调的组蛋白手征性模型，模拟了核小体手征性的形成。发现DNA的缠绕方向强烈依赖于组蛋白的手征性。结果还显示出环境温度对核小体手征性有重要影响，提高温度可打破核小体的手征性。

我们模拟了由染色质重组复合体引起的DNA弯曲对组蛋白定向滑移的影响。结果表明，在核小体一边的DNA上产生一个弯曲环后，组蛋白八聚体会向这个弯曲环滑动，直至这个弯曲环消失。DNA弯曲环的大小是影响组蛋白八聚体会滑动的重要因素。

通过改变DNA与组蛋白八聚体之间的相互作用力，我们研究了组蛋白修饰（磷酸化、乙酰化、甲基化）对核小体结构的影响。布朗动力学结果显示核小体的结构稳定性很敏感地依赖于相互作用力的大小。DNA从修饰后的组蛋白八聚体上一圈一圈地解离下来。我们还研究了温度影响、DNA断点的影响以及修饰后的组蛋白八聚体与非修饰组蛋白八聚体的竞争效应。解释了DNA断点处的磷酸化核小体更容易解离的现象。

42．金属离子耦合的锌指蛋白折叠

王 炜

南京大学 物理系

wangwei@nju.edu.cn

金属离子一类重要的辅助因子，由于缺少一个合理的描述金属离子与蛋白质相互作用的理论模型，金属离子辅助的蛋白质折叠问题目前还仅仅局限于实验研究。通过将量子化学的计算结果整合到经典的分子动力学中，以及考虑金属离子诱导的去质子化等效应和金属离子诱导的极化效应。我们研究了典型的金属蛋白“锌指蛋白”的折叠过程，给出了金属离子与蛋白质结合的详细路径，以及金属离子的结合在蛋白质折叠中的作用。发现锌离子不仅可以稳定锌指蛋白的天然态结构，并且参与整个蛋白质折叠过程，调控蛋白质二级结构的折叠顺序与相对稳定性。这种金属离子在蛋白质二级结构折叠中的作用是由疏水核的形成所介导。同时，计算结果还表明锌指蛋白折叠过程中存在错误配位与配体交换现象。

43．Folding pathways of beta-hairpin

肖奕

华中科技大学物理系

yxiao@mail.hust.edu.cn

After ten-year investigations, the folding mechanisms of beta-hairpins are still under debate. Experiments strongly support zip-out pathway, while most simulations prefer the hydrophobic collapse model (including middle-out and zip-in pathways). We show that all pathways can occur during the folding of beta-hairpins but with different probabilities. The zip-out pathway is the most probable one. This is in agreement with the experimental results. We came to our conclusions by thirty-eight 100-ns room-temperature all-atom molecular dynamics simulations and 2700 20-ns United-Residue (UNRES) Langevin dynamics simulations of the beta-hairpin trpzip2. Our results may help to clarify the inconsistencies in the current pictures of β-hairpin folding mechanisms.

44．Single-Molecule Enzymology with Dynamic Disorder

薛晓川

清华大学高等研究中心

xuexc05@mails.tsinghua.edu.cn

The classic Michaelis-Menten equation describes the catalytic activities for ensembles of enzyme molecules very well. But recent single-molecule experiment showed that the waiting time distribution and other properties of single enzyme molecule were not consistent with the prediction based on the view point of ensemble. It has been contributed to the slow conformational changes of single enzyme in the catalytic processes. In this work we study the general dynamics of single enzyme in the presence of dynamic disorder. We find that, within the time separation regimes, i.e., the slow reaction and nondiffusion limits,

Michaelis-Menten equation exactly holds. Particularly, by employing the decoupling approximation we demonstrate analytically that the classic Michaelis-Menten equation is still an excellent approximation in the presence of general dynamic disorder. Especially, with this novel concept, we can understand the experimental results of a recent force-stretched single-molecule enzymatic reaction.

45．Experimental and theoretical studies of DNA micromechanics

严洁

National University of Singapore

phyyj@nus.edu.sg

The long DNA molecules are tightly compacted in cells, bacterial, and viruses. This tight folding is done at a cost of a huge DNA bending energy since DNA is rigid at short lengths. Using single-molecule manipulation and imaging methods, here we present our recent studies of the micromechanics of tightly bent DNAs. We show that local DNA defects may appear under above threshold bending curvature. Further investigations show that the defects are critical to understand recently reported anomalous DNA elasticity observed for short DNA under tight bending conditions. Our methods can be easily applied to the studies the micromechanics of other bio-molecules in cells.

46．A Logic-Based Technique that Characterizes the Class of Boolean Networks Producing a Given Biological Pathway

曾辰

George Washington University/华中科技大

chenz@gwu.edu

This talk considers Boolean models of biological networks as commonly applied to gene regulation. In such networks, any given start state leads deterministically to a sequence of states that end in an attractor or repeat in a cycle. Some recent work have constructed Boolean networks to explain particular biological pathways such as the cell cycle, in which the sequence of states is known to correspond to a particular biological function, and which raise interesting questions: how many networks produce a given sequence? What makes the naturally occurring network unique amongst these? This talk focuses on a logic-based technique to analyze such networks and, as a result, identifies an interesting property of the class of networks modeling the cell-cycle that helps address the latter question.

47．Local-majority-rule dynamics: Influence of network structure and dynamics-driven structural evolutions

周海军

中国科学院理论物理研究所

zhouhj@itp.ac.cn

The mutual influence of structure and dynamical processes in a complex networked system is an active yet challenging research topic. In the present report we approach this problem by studying a simple model system, namely the local majority-rule (LMR) dynamics on an evolving network. We first show analytically and by computer simulation that the structure of the network can have a qualitative influence on the typical relaxation time of the LMR dynamics, and that scale-free networks with decaying exponent $\gamma$ in the tiny range of $2< \gamma <2.5$ are particularly

efficient for the LMR process. Then we demonstrated that, under simple local rules of dynamics-structure feedback, the LMR dynamics can slowly drive the underlying network into a highly heterogeneous structure with high clustering coefficient and scale-free-like degree distributions. Most interestingly, a global hub emerges spontaneously in the network, which has direct interaction with a major fraction of all the other vertices of the network.

This work is done in collaboration with Reinhard Lipowsky and Zhen Shao.

References:

H. J. Zhou and R. Lipowsky, PNAS, 102 (2005), 10052-10057.

H. J. Zhou and R. Lipowsky, JSTAT, P01009 (2007).

Z. Shao and H. J. Zhou, arXiv: 0804.3181v1 (2008).

48．Effect of the Ordered Water on Protein Folding: An Off-Lattice Go-Like Model Study

左光宏

复旦大学物理系

ghzuo@fudan.edu.cn

Recent experiments have shown that the water molecules confined on the surfaces of some substrates, including the surfaces of cellular components in tissues and cells, form icelike ordered structures. Here, the effect of this ordered water on protein folding is studied quantitatively by using an off-lattice Go-like model. Our results show that the ordered water significantly promotes both the stability and the folding rate of proteins. Moreover, it is found that both the stability and the folding rate with respect to the size of the confined space can be characterized by negative exponential laws with close exponential parameters for different proteins.

49．Genome-Wide Identification and Evolutionary Analysis of the Plant Specific

SBP-box Transcription Factor Family

An-Yuan Guo, Qi-Hui Zhu, Xiaocheng Gu, Song Ge, Ji Yang, Jingchu Luo（罗静初）

北京大学生物信息中心

luojc@pku.edu.cn

We made genome-wide analyses to explore the evolutionary process of the SBP-box gene family. We identified 120 SBP-box genes from nine species representing the main green plant lineages: green alga, moss, lycophyte, gymnosperm and angiosperm. A maximum-likelihood phylogenetic tree was constructed using the protein sequences of the DNA-binding domain of SBP-box genes (SBP-domain). Our results revealed that all SBP-box genes of green alga clustered into a single clade (CR group), while all genes from land plants fell into two distinct groups. Group I had a single copy in each species except for poplar while group II had several members in each species and can be divided into several subgroups. The SBP-domain encoded by all SBP-box genes possesses two zinc fingers. The C-terminal zinc finger of both group I and group II had the same C2HC motif while their N-terminal zinc finger showed different signatures, C4 in group I and C3H in group II. The patterns of exon-intron structure in Arabidopsis and rice SBP-box genes were consistent with the phylogenetic results. A target site of microRNA miR156 was highly conserved among land plant SBP-box genes. Our results suggested that the SBP-box gene family might have originated from a common ancestor of green plants, followed by duplication and divergence in each lineage including exon-intron loss processes.

50．PlantTFDB: a comprehensive plant transcription factor database.

Guo AY, Chen X, Gao G, Zhang H, Zhu QH, Liu XC, Zhong YF, Gu X, He K, Luo J. （罗静初）

北京大学生物信息中心

luojc@pku.edu.cn

We made genome-wide analyses to explore the evolutionary process of the SBP-box gene family. We identified 120 SBP-box genes from nine species representing the main green plant lineages: green alga, moss, lycophyte, gymnosperm and angiosperm. A maximum-likelihood phylogenetic tree was constructed using the protein sequences of the DNA-binding domain of SBP-box genes (SBP-domain). Our results revealed that all SBP-box genes of green alga clustered into a single clade (CR group), while all genes from land plants fell into two distinct groups. Group I had a single copy in each species except for poplar while group II had several members in each species and can be divided into several subgroups. The SBP-domain encoded by all SBP-box genes possesses two zinc fingers. The C-terminal zinc finger of both group I and group II had the same C2HC motif while their N-terminal zinc finger showed different signatures, C4 in group I and C3H in group II. The patterns of exon-intron structure in Arabidopsis and rice SBP-box genes were consistent with the phylogenetic results. A target site of microRNA miR156 was highly conserved among land plant SBP-box genes. Our results suggested that the SBP-box gene family might have originated from a common ancestor of green plants, followed by duplication and divergence in each lineage including exon-intron loss processes.

51．Study of DNA bending elasticity by AFM Imaging of circular DNA

陈虎

新加坡国立大学物理系

phych@nus.edu.sg

Unusual DNA elasticity observed under tight bending conditions has been debated and has drawn great attentions from biologists and biophysicists. We present a new experimental evidence displaying unusual DNA bending elasticity by analyzing the shape distributions of DNA minicircles of size 189 and 378 base-pairs which are relaxed in 2D surface. The distributions are found different from the predictions by the canonical WLC model. The bending energy of DNA is smaller than WLC under the sharp bending conditions, which indicates that it is not so difficult to form sharp bending conformations as predicted by WLC model.Different non-linear bending elasticity models are discussed to explain all related experiments about DNA bending elasticity.

52．人类灵长类特有锌指蛋白ZNF480在肌管分化和形成过程中的多级调控作用

吴秀山

湖南师范大学心脏发育研究中心

Xiushanwu2003@yahoo.com.cn

灵长类特有锌指蛋白约占人类基因组中最大蛋白家族－Kruppel锌指蛋白的三分之一，至今尚无任何关于这些基因功能性研究的报道（Aaron T.等，2006）。我们选择小鼠C2C12细胞系模型，以灵长类特有锌指基因ZNF480为代表，研究该类蛋白的蛋白结合位点与功能的进化关系。研究结果表明，人类 ZNF480基因的mRNA 和蛋白表达水平随小鼠细胞模型的肌管分化和形成过程而上调，明显促进小鼠C2C12细胞系的肌管的生成，说明ZNF480尽管已进化为灵长类特有锌指基因，其调控哺乳类肌肉细胞分化的功能仍然得以保留。为了进一步探讨灵长类ZNF480蛋白调控哺乳类肌肉细胞分化的分子调控机制，我们研究了ZNF480蛋白与小鼠/人类myogenin启动子上的保守结合位点的关系，发现ZNF480蛋白能与小鼠/人类myogenin启动子的保守结合位点结合，表明ZNF480蛋白调控哺乳类肌肉细胞分化的功能是通过myogenin启动子的结合位点的保守性进化而实现的。同时，我们发现ZNF480蛋白和E12/MyoD蛋白在肌肉特异性基因MCK的启动子上形成了新的结合位点，ZNF480蛋白是与E12/MyoD蛋白形成复合体，结合在MCK启动子上的新结合位点上，共同增强MCK的转录活性，从而促进小鼠肌细胞分化和肌管的形成。这些结果证实了我们克隆的人类灵长类特有基因ZNF480在促进小鼠肌细胞分化和肌管形成中的多级调控作用，为解释灵长类特有锌指蛋白的功能进化提供了新的模型。

53．从衰老生化本质看“上医治未病”的科学道理

印大中

湖南师范大学生命科学学院

dazhongyin@hotmail.com

尽管“上医治未病”是中医对待疾病和健康问题的一个突出的思维优势，但解读其中隐含的科学原理却是中西医结合生命科学所面临的极大的难题。本专题以系统生物医学和老年医学的最新研究进展为基础，以（能量）代谢组学和蛋白质表达后在衰老过程中的生化变化规律及其相互作用的专业知识为启迪，将“中医治本”与生命在应激过程中出现的“亚健康”生理生化过程贯通思考，为传统中医体系中诸多“防重于治”的医疗措施和理论提出了现代科学的解释。

54．葡萄糖和RyR通道调控的胰腺β细胞

詹璇，贾亚

华中师范大学物理学院

zhanx@phy.ccnu.edu.cn

我们的主要工作是，首次将葡萄糖浓度和Ryanodine受体（RyR）通道引入到胰腺β细胞模型中，讨论了葡萄糖浓度和RyR通道对胰腺β细胞膜电位振荡形式的影响。结果表明细胞对葡萄糖浓度变化的响应比激活RyR通道时更加快速，而以上两种方法都可以使膜电位从超极化的静息态变成爆发式振荡的电活性。当葡萄糖浓度低于刺激值时适量的激活RyR通道也能使膜电位发生爆发式振荡以及引发细胞液内自由Ca^2＋平均浓度的增加。特别是，发现适当激活RyR通道时膜电位会出现一种复杂振荡，并且这种复杂振荡形式可能比一般的爆发式振荡能更有效的引发胰岛素分泌。我们还对模型进行动力学分析以帮助了解参数变化引发振荡形式变化的原因。

55．Intrinsic peroxidase-like activity of ferromagnetic nanoparticles and application in an immunoassay

阎锡蕴

中国科学院生物物理研究所

yanxy@sun5.ibp.ac.cn

Nanoparticles that contain magnetic materials, such as magnetite (Fe₃O₄), are particularly useful for imaging and separation techniques. Since these nanoparticles are generally considered to be biologically and chemically inert, they are typically coated with metal catalysts, antibodies or enzymes to increase their functionality as separation agents. Here, we report that magnetite nanoparticles in fact possess an intrinsic enzyme mimetic activity similar to that found in natural peroxidases, which are widely used to oxidize organic substrates in the treatment of wastewater or as detection tools. Based on this finding, we have developed a novel immunoassay in which antibody-modified magnetite nanoparticles provide three functions: capture, separation and detection. The stability, ease of production and versatility of these nanoparticles makes them a powerful tool for a wide range of potential applications in medicine, biotechnology and environmental chemistry.

56．A charge driven molecular water pump inspired by the structure of biological channels (aquaporins)

方海平

中国科学院上海应用物理研究所

Fanghaiping@sinap.ac.cn

Understanding and controlling the transport of water across nanochannels is of great importance for designing novel molecular devices, machines and sensors and has wide applications, including the desalination of seawater. Nano-pumps driven by electric or magnetic fields can transport ions and magnetic quanta, but water is charge-neutral and has no magnetic moment. On the basis of molecular dynamics simulations, we propose a design for a molecular water pump. The design uses a combination of charges positioned adjacent to a nanopore, and is inspired by the structure of channels in the cellular membrane that conduct water in and out of the cell (aquaporins). The remarkable pumping ability is attributed to the charge dipole-induced ordering of water confined in the nanochannels where water can be easily driven by external fields in a concerted fashion. These findings may provide possibilities for developing water transport devices that function without osmotic pressure or a hydrostatic pressure gradient.

57．单个RNA分子力致折叠和去折叠时间序列的Bayesian分析

柳飞

清华大学高等研究中心，北京

liufei@mail.tsinghua.edu.cn

单个RNA分子力致折叠和去折叠光阱实验可以获得大量的分子延展时间序列。从这些序列中推断出RNA分子内在物理参数是个相当有意义的生物物理学问题。在这个工作中我们理论考察了这种可能性。我们首先构建了该实验系统的一个粗粒化理论模型，并在此模型的基础上，提出了一个基于Monte Carlo Markov链的Bayesian分析方法。我们的计算表明，该方法在推断分子内在物理参数是相当有效和精确的。

58．Exact Shape Equation of Solid Lipid Monolayer Domain : A Primary Model for Raft Formation in Membranes

欧阳钟灿

中国科学院理论物理研究所

oy@itp.ac.cn

Solid lipid monolayer domain surround by a fluid phase is studied by the equilibrium between line tension and long range dipole-dipole interaction. An exact domain shape equation is derived in form without introducing an artificial cutoff distance between dipoles. By introducing a cut-off of interaction distance between molecular dipoles to prevent divergence of the terms relating electrostatic dipole-dipole energy we obtained a approximate shape equation. From the equation we have found its analytic solutions among which a kinked shape solution (i.e., a cusp appears in the boundary) is nicely confirmed in many experimental observations in lipid monolayer. It reveals that the electrostatic dipole-dipole energy, a double line integral same as the Neumann’s formula for self-inductance of a single coil, can be regarded as the formation mechanism of raft in membranes.

References:

[1] M. Iwamoto and Ou-Yang Zhong-can, Phys. Rev. Lett. 93, 206101 (2004)

[2] M. Iwamoto, Liu Fei, and Ou-Yang Zhong-can, J. Chem. Phys. 125, 224701 (2006)