Jakobsson The 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.
