Geometry and the discovery of new ligands

Computer-aided drug design is a significant component of the rational approach to pharmaceutical drug design. Chemists now consider the geometric and chemical characteristics of molecules early in the design process in an effort to quickly identify ligands that have good chances of becoming potent pharmaceutical drugs, Computer assistance is not only helpful but also necessary to narrow down the search for potential ligands. Depending on the level of accuracy desired to model drug action, detailed quantum mechanical methods or approximate molecular mechanics methods are used. Even when simple approximations are made, efficient approaches are needed to compute, among other things, molecular surfaces and molecular volume, models of receptor active sites, reasonable dockings of ligands inside protein cavities, and geometric invariants among different ligands that exhibit similar activity. This paper surveys several problems and approaches in the area of computer-aided pharmaceutical drug design and draws analogies with problems from robotics and computational geometry.