S. Handschuh et al., SUPERPOSITION OF 3-DIMENSIONAL CHEMICAL STRUCTURES ALLOWING FOR CONFORMATIONAL FLEXIBILITY BY A HYBRID METHOD, Journal of chemical information and computer sciences, 38(2), 1998, pp. 220-232
Citations number
42
Categorie Soggetti
Computer Science Interdisciplinary Applications","Computer Science Information Systems","Computer Science Interdisciplinary Applications",Chemistry,"Computer Science Information Systems
The superposition of three-dimensional structures is the first task in
the evaluation of the largest common three-dimensional substructure o
f a set of molecules. This is an important step in the identification
of a pharmacophoric pattern for molecules that bind to the same recept
or. The superposition method described here combines a genetic algorit
hm with a numerical optimization method. A major goal is to adequately
address the conformational flexibility of ligand molecules. The genet
ic algorithm optimizes in a nondeterministic process the size and the
geometric fit of the substructures. The geometric fit is further impro
ved by changing torsional angles combining the genetic algorithm and t
he directed tweak method. This directed tweak method is based on a num
erical quasi-Newton optimization method. Only one starting conformatio
n per molecule is necessary. Molecules having several rotatable bends
and quite different initial conformations are modified to find large s
tructural similarities. A set of angiotensin II antagonists is investi
gated to illustrate the performance of the method.