MODELING & STIMULAT OF STRUCT FUNCT & SELECTIVITY OF BIOL SYS

我们实验室研究的总体理论基础是 发现生物的结构、动态和电子决定因素 以生理功能为基础的过程，使用 理论和计算生物物理学。我们寻求的是分子水平， 对结构-功能关系的机械性理解 在有关结构和性能的实验信息中 细胞成分和生理机制。我们的方法使用 基于经典和基本定律的定义良好的算法 量子物理学；它们包括计算机辅助的分子建模 分子的结构、性质及计算模拟 机械装置。这些理论研究旨在补充 提供关于系统的机械性见解的实验 不断增加的规模和复杂性，并指导有针对性的实验 对细胞过程和功能的探索 合作研究。为了促进 理论和实验研究，下面描述的项目是 与实验小组密切合作开展了这项工作。这个 我们使用的理论方法也在扩展、改进和测试 在研究生物分子系统方面。这些项目的目标是 方法论的发展是为了扩大问题的范围， 可以通过计算方法进行研究，加深对 可以从计算中获得具有新颖性和精确度的 分析方法，并允许快速计算 具有直接的实验相关性。正如我们的 通过出版，我们的工作涉及当前研究的主要领域。一个 我们研究不同生物过程的统一主题是 实现对分子触发机制的分子理解 识别并导致信号转导。目前，我们正在研究 三个主要领域的结构特殊性和动态 过程决定了基本的生理机制如下：i) 细胞信号转导机制中的特异性决定因素 通过配基识别和受体反应；ii)解码和 通过EF-Hand钙结合蛋白处理钙信号； 和iii)蛋白质产生的特异性和功能触发 与DNA结合。第四个领域包括提法和 用于快速计算机模拟的隐式溶剂模型的发展 关于生物系统的。

The overall rationale of the research in our laboratory is to discover structural, dynamic and electronic determinants of biological processes that underlie physiological functions, using methods of theoretical and computational biophysics. We seek a molecular level, mechanistic understanding of structure-function relationships anchored in experimental information about structures and properties of cellular components and physiological mechanisms. Our approaches use well-defined algorithms based on the fundamental laws of classical and quantum physics; they include computer assisted modeling of molecular structure and properties and computational simulations of molecular mechanisms. The theoretical studies are designed to complement experimentation in providing mechanistic insights about systems of ever increasing size and complexity, and to guide pointed experimental exploration of cellular processes and functions in numerous collaborative studies. To facilitate the interaction between the theoretical and experimental studies, the projects described below are carried out in close collaboration with experimental groups. The theoretical methods we use are also being expanded, refined and tested in the study of biomolecular systems. The goals of these methodological developments are to extend the scope of problems that can be studied by computational approaches, deepen the insights that can be obtained from the computations with novel and sophisticated methods of analysis, and allow the fast calculation of properties that are of direct experimental relevance. As documented in our publications, our work addresses major areas of current research. A unifying theme in our studies of diverse biological processes is to achieve a molecular understanding of mechanisms triggered by molecular recognition and leading to signal transduction. Currently, we study structural specificity and dynamics in three main areas in which such processes determine essential physiological mechanisms as follows: i) The determinants of specificity in mechanisms of cellular signaling through ligand recognition and receptor response; ii) the decoding and processing of Ca2+ signals through the EF-hand Ca-binding proteins; and iii) the specificity and functional trigger produced by protein binding to DNA. A fourth area comprises the formulation and development of an implicit solvent model for fast computer simulations of biological systems.