Atomic-Level Simulation and Modeling of Biomacromolecules.

Abstract

In principle, all the problems in biology could be solved by solving the time-dependent Schroedinger equation (quantum mechanics, QM). This would lead to a detailed under-standing of the role that molecular-level interactions play in determining the fundamental biochemistry at the heart of biology and pharmacology. The difficulty is the vast range of length and time scales, from a nitrous oxide molecule to an organ (heart, lung), which makes a QM solution both impractical and useless. It is impractical because there are too many degrees of freedom describing the motions of the electrons and atoms, whereas in the functioning of an organ it may be only the rate of transfer across some membrane. The solution to both problems is the hierarchical strategy outlined in figure 6.1. We average over the scale of electrons (from QM) to describe the forces on atoms (the force field, FF), then average over the dynamics of atoms (molecular dynamics, MD) to describe the motions of large biomolecules, then average over the molecular scale to obtain the properties of membranes, then average over the components in a cell, then average over the cells to describe a part of an organ. The strategy is to develop a methodology for going between these various levels so that first principle’s theory can be used to predict the properties of new systems.

Group Members

William A. Goddard III

Charles and Mary Ferkel Professor