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Anti‐insulin antibody structure and conformation. I. Molecular modeling and mechanics of an insulin antibody
Author(s) -
Nell Laura J.,
McCammon J. Andrew,
Subramaniam Shankar
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.360320104
Subject(s) - chemistry , homology modeling , amino acid , side chain , molecular model , peptide sequence , epitope , protein structure , crystallography , molecular graphics , molecular mechanics , stereochemistry , molecular dynamics , antibody , van der waals force , immunoglobulin light chain , biochemistry , molecule , computational chemistry , genetics , biology , organic chemistry , artificial intelligence , computer science , gene , computer graphics , enzyme , polymer
A knowledge‐based three‐dimensional model of an anti‐insulin antibody, 125, was constructed using the structures of conserved residues found in other known crystallographic immunoglobulins. Molecular modeling and mechanics were done with the 125 amino acid sequences using QUANTA and CHARMm on a Silicon Graphics 4D70GT workstation. A minimal model was made by scaffolding using crystallography coordinates of the antibody HyHEL‐5, because it had the highest amino acid sequence homology with 125 (84% light chain, 65% heavy chain). The three hypervariable loop turns that are longer in 125 than in HyHEL‐5 (L1, L3, and H3) were modeled separately and incorporated into the HyHEL‐5 structure; then other amino acid substitutions were made and torsions optimized. The 125 model maintains all the structural attributes of an antibody and the structures conserved in known antibodies. Although there are many polar amino acids (especially serines) in this site, the overall van der Waals surface shape is determined by positions of aromatic side chains. Based on this model, it is suggested that hydrogen bonding may be key in the interaction between the human insulin A chain loop antigenic epitope and 125.