Biology Reference
In-Depth Information
Chapter 10
Molecular Modeling of Proteins:
From Simulations to Drug Design
Applications
Vincent Zoete, Michel Cuendet, Ute F. Röhrig,
Aurélien Grosdidier and Olivier Michielin
1. Introduction
Over the last 30 years, molecular modeling has become an essential tool
to study the properties of large molecular systems in various fields of
chemistry, biology, and medicine. Nowadays, molecular modeling is rou-
tinely used to understand the molecular function of complex protein
systems, or to perform rational protein and drug design. The range of
examples includes the detailed understanding of ion conduction through
the potassium channel, 1 the mechanism of action of the GroEL chaper-
onin, 2 electron transfer in DNA molecules, 3 the estimation of protein
pKa's, 4 the design of improved immunoglobulin, 5 and the design of a
small-molecule inhibitor of the Bcr-Abl aberrant tyrosine kinase. 6
As such, molecular modeling aims at bridging the gap between the static
structure provided by X-ray or nuclear magnetic resonance (NMR)
experiments and the biological function.
The molecular dynamics (MD) method was first introduced by Alder
and Wainwright in the late 1950s 7,8 to simulate the dynamics of 150
argon atoms described as interacting hard spheres. Many important
247
Search WWH ::




Custom Search