KDI: An Integrated Computational Environment for Studying Ion Movement in Biological Systems

KDI：用于研究生物系统中离子运动的集成计算环境

• 批准号: 9873199
• 负责人: Eric Jakobsson
• 金额: $ 110万
• 依托单位: University of Illinois at Urbana-Champaign
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-10-01 至 2002-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9873199&HistoricalAwards=false
• 关键词: KDI; Integrated; Computational; Environment; Studying

9873199JakobssonThe overall objective of this project is to make it possible to predict the detailed function of a protein from its structure and internal motion. Protein structure is, of course, fundamental to protein function, but equally important are the internal thermal motions that a protein continually undergoes. The basic problem is that protein structure is so complicated, and proteins have so many potential ways to move, that it is impossible to do a "brute force" simulation of all the possible protein motions and catalog their effects. The solution is to break the problem of describing protein motion into a hierarchy of problems, and treat each level of the hierarchy separately, moving from the most detailed to more "coarse-grained" descriptions. In each case, the numerical results from the most detailed calculation will be used as parameters for a more coarse-grained calculation. In order to predict function from structure, three levels of description will be developed: 1) quantum chemistry, 2) classical molecular dynamics, and 3) kinetic theory. The results from the kinetic theory will be compared directly with experiment. To validate this approach, work will focus on ion channels, the membrane proteins that permit ions to cross biological membranes. All software developed in the course of the project will be embedded in the Biology Workbench (bioweb.ncsa.uiuc.edu). The Biology Workbench is a Web-based computing environment for molecular biology that assembles database and analysis programs from disparate sources into effectively a single program that any user can easily customize to his or her own needs.

9873199Jakobsson这个项目的总体目标是使从其结构和内部运动中预测蛋白质的详细功能。蛋白质结构当然是蛋白质功能的基础，但同样重要的是蛋白质不断发生的内部热运动。 基本问题是蛋白质结构是如此复杂，并且蛋白质具有许多潜在的移动方法，因此无法对所有可能的蛋白质运动进行“蛮力”模拟并对其效应进行分类。 解决方案是将描述蛋白质运动描述为问题的层次结构的问题，并分别处理层次结构的每个级别，从最详细的描述到更“粗粒”的描述。 在每种情况下，最详细的计算的数值结果将用作更粗糙的计算的参数。 为了从结构中预测功能，将开发三个级别的描述：1）量子化学，2）经典分子动力学和3）动力学理论。 动力学理论的结果将直接与实验进行比较。 为了验证这种方法，工作将重点放在离子通道，即允许离子越过生物膜的膜蛋白上。 该项目过程中开发的所有软件都将嵌入生物学工作台（bioweb.ncsa.uiuc.edu）中。 生物学工作台是一个用于分子生物学的基于网络的计算环境，该计算环境将数据库和分析程序从不同的来源组装成有效的单个程序，任何用户都可以轻松自定义其自己的需求。