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Systematic drug receptor mapping: A new approach to the analysis of conformational energy calculations of flexible molecules with application to dopaminergic and adrenergic agonists
Author(s) -
Sanathanan Lilly,
Danaher Elizabeth,
Kim KiHwan,
Martin Yvonne
Publication year - 1987
Publication title -
journal of computational chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.907
H-Index - 188
eISSN - 1096-987X
pISSN - 0192-8651
DOI - 10.1002/jcc.540080802
Subject(s) - dihedral angle , molecule , probability distribution , torsion (gastropod) , chemistry , boltzmann constant , potential energy surface , computational chemistry , statistical physics , physics , mathematics , thermodynamics , quantum mechanics , medicine , hydrogen bond , surgery , statistics
The computer program PRODIS is used to find low energy conformations of flexible molecules by searching the potential energy surface(s) of one or more torsion angles via rigid rotation. The n ‐dimensional grid of energy versus torsion angles is then converted to a Boltzman probability distribution, with the probability being represented not as a function of torsion angle, but rather a distance between two atoms. These atoms are chosen by comparison with a known, active analogue in which certain atoms have previously been determined as requirements for drug activity. PRODIS produces a list of low energy conformations, their corresponding interatomic distances and the Boltzman probability for each distance ±0.125, as well as the total probability for each conformation. The user also specifies a target interatomic distance and range (usually derived from a more rigid analogue) for which PRODIS lists all conformations and their Boltzman probability that meet this distance.