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VRI: 3D QSAR at variable resolution
Author(s) -
Crippen Gordon M.
Publication year - 1999
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/(sici)1096-987x(19991115)20:14<1577::aid-jcc11>3.0.co;2-i
Subject(s) - chemistry , quantitative structure–activity relationship , overfitting , computational chemistry , partial least squares regression , resolution (logic) , conformational isomerism , molecular descriptor , molecule , stereochemistry , biological system , artificial intelligence , computer science , machine learning , organic chemistry , artificial neural network , biology
VRI (Variable Resolution Invariants) is a new approach to quantitative structure–activity relations that makes use of three‐dimensional features of molecules at different levels of spatial resolution as well as levels of resolution in atomic properties. These descriptors are independent of any numbering of the atoms of a molecule. They are also independent of rigid translation and rotation of a given conformer, which avoids problems with aligning different molecules or docking them with a receptor site model. Steric effects, stereospecificity, substituent effects, lipophilicity, and conformational flexibility are all dealt with in a single, natural formalism. Simple datasets can be fitted using a small number of descriptors corresponding to low‐resolution descriptions of the molecules. More complicated data can require additional descriptors that recognize finer details of three‐dimensional structure and physico‐chemical properties. Overfitting due to the large number of descriptors is handled by partial least‐squares analysis with crossvalidation. Performance in fitting and predicting is demonstrated on some simple illustrative cases, and on three standard sets of real data: steroids binding to human corticosteroid binding globulin and testosterone binding globulin, and inhibitors of dihydrofolate reductase. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 1577–1585, 1999