COMPARATIVE MOLECULAR-FIELD ANALYSIS OF PROTEIN-TYROSINE-PHOSPHATASE LOW-MOLECULAR-WEIGHT SUBSTRATES

A set of 25 low-molecular-weight substrates for protein tyrosine phosp hatase PTP1 has been investigated by comparative molecular field analy sis (CoMFA). The quality of the model was assessed by cross-validation s, predictions for a test set of substrates, bootstrapping, randomizat ion of biological data, grid characteristics tests, and comparison wit h the X-ray-determined binding site of a closely related enzyme. The C oMFA study provides new insight into the steric and electrostatic fact ors influencing binding around the active site in protein tyrosine pho sphatase and complements existing information available from X-ray dat a. (C) 1998 National Research Council of Canada. Published by Elsevier Science B.V. All rights reserved.