Structure-aided drug design: crystallography and computational approaches.

Abstract

Ideally, a drug that effectively attacks a specific target will be efficacious with few or no side effects. Historically, drug development has relied on a structure-activity sequential (trial-and-error) approach, testing many compounds and observing their pharmacologic effects. More recently, molecular biologists have investigated a new approach to drug design: starting with a specific target, determining what types of molecules would have a desired effect on that target and then constructing molecules that fit those criteria. Structure-aided drug design is a tool used in this new approach, which involves using crystallographic data and computer processing to describe a molecule precisely--in terms of all binding, Van der Waal's and electrostatic interactions--as a computational entity. The goal of this computational approach is to determine whether a molecule will bind to a target molecule and the character of the ligand interaction.