MOLMAKER: de novo generation of 3D databases for use in drug design.
A program, MOLMAKER, is described which, in conjunction with a 2D-3D conversion program and 3D database software, can generate de novo 3D databases to aid in drug design. MOLMAKER is based upon graph-theoretical techniques for vertex degree set generation and constructive enumeration of molecular graphs. The generated molecular graphs are then functionalised in a probabilistic manner but in accordance with various constraints specified by the user. The resulting connection tables can be converted into 3D structures by commercial software and loaded into a 3D database for pharmacophore searching. The utility of MOLMAKER is illustrated by two examples of interest from the recent scientific literature: the design of novel protein kinase C agonists and of a bridging ligand for cyclophilin-calcineurin.
Clark
D E
DE
Proteus Molecular Design Ltd., Macclesfield, Cheshire, United Kingdom.
Firth
M A
MA
Murray
C W
CW
D000591:Amino Acid Isomerases / Q000737:chemistry; D019703:Calcineurin; D002148:Calmodulin-Binding Proteins / Q000737:chemistry; D002352:Carrier Proteins / Q000737:chemistry; D016208:Databases, Factual; D015195:Drug Design; D008024:Ligands; D015394:Molecular Structure; D019696:Peptidylprolyl Isomerase; D010749:Phosphoprotein Phosphatases / Q000737:chemistry; D011493:Protein Kinase C / Q000378:metabolism; D012984:Software
D002148:Calmodulin-Binding Proteins; D002352:Carrier Proteins; D008024:Ligands; D011493:Protein Kinase C; D019703:Calcineurin; D010749:Phosphoprotein Phosphatases; D000591:Amino Acid Isomerases; D019696:Peptidylprolyl Isomerase