Field-based similarity forcing in energy minimization and molecular matching.
A new field-based similarity forcing procedure for matching conformationally-flexible molecules is presented. The method extends earlier work on similarity matching of molecules based upon the program MIMIC, by directly coupling a similarity function to a molecular mechanics force field. In this way conformational energetics are fully accounted for in the similarity matching process. Simultaneous similarity/conformational searches can then be undertaken within a Monte Carlo or molecular dynamics framework. Here, a Monte Carlo approach is used to provide a simple example of two HIV-1 reverse transcriptase inhibitors, nevirapine and alpha APA, that illustrates the basic characteristics of the method and suggests areas for further investigation.
Blinn
J R
JR
Pharmacia & Upjohn, Kalamazoo, MI 49007, USA.
Rohrer
D C
DC
Maggiora
G M
GM
D002151:Calorimetry; D015195:Drug Design; D054303:HIV Reverse Transcriptase / Q000737:chemistry*; D008958:Models, Molecular; D008968:Molecular Conformation; D009010:Monte Carlo Method; D019829:Nevirapine / Q000737:chemistry*; D011487:Protein Conformation; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry*; D012984:Software; D055672:Static Electricity; D013816:Thermodynamics
D018894:Reverse Transcriptase Inhibitors; D019829:Nevirapine; D054303:HIV Reverse Transcriptase