Flexibases: a way to enhance the use of molecular docking methods.
Specially expanded databases containing three-dimensional structures are created to enhance the utility of docking methods to find new leads, i.e., active compounds of pharmacological interest. The expansion is based on the automatic generation of a set of maximally dissimilar conformations. The ligand receptor system of methotrexate and dihydrofolate reductase is used to demonstrate the feasibility of creating flexibases and their utility in docking studies.
Kearsley
S K
SK
Department of Molecular Systems, Merck Research Laboratories, Rahway, NJ 07065.
Underwood
D J
DJ
Sheridan
R P
RP
Miller
M D
MD
D000465:Algorithms; D001665:Binding Sites; D017076:Computer-Aided Design; D016208:Databases, Factual; D015195:Drug Design; D005493:Folic Acid Antagonists; D046911:Macromolecular Substances; D008727:Methotrexate / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011487:Protein Conformation; D012984:Software; D013762:Tetrahydrofolate Dehydrogenase / Q000737:chemistry; D013816:Thermodynamics
D005493:Folic Acid Antagonists; D046911:Macromolecular Substances; D013762:Tetrahydrofolate Dehydrogenase; D008727:Methotrexate