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Anti‐insulin antibody structure and conformation. II. Molecular dynamics with explicit solvent
Author(s) -
Tanner John J.,
Nell Laura J.,
McCammon J. Andrew
Publication year - 1992
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.360320105
Subject(s) - solvation , molecular dynamics , chemistry , hydrogen bond , side chain , molecule , solvent , molecular model , crystallography , computational chemistry , stereochemistry , biochemistry , organic chemistry , polymer
Molecular dynamics at 300 K was used as a conformation searching tool to analyze a knowledge‐based structure prediction of an anti‐insulin antibody. Solvation effects were modeled by packing water molecules around the antigen binding loops. Some loops underwent backbone and side‐chain conformational changes during the 95‐ps equilibration, and most of these new, lower potential energy conformations were stable during the subsequent 200‐ps simulation. Alterations to the model include changes in the intraloop, main‐chain hydrogen bonding network of loop H3, and adjustments of Tyr and Lys side chains of H3 induced by hydrogen bonding to water molecules. The structures observed during molecular dynamics support the conclusion of the previous paper that hydrogen bonding will play the dominant role in antibody‐insulin recognition. Determination of the structure of the antibody by x‐ray crystallography is currently being pursued to provide an experimental test of these results. The simulation appears to improve the model, but longer simulations at higher temperatures should be performed.