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Study of the insulin dimerization: Binding free energy calculations and per‐residue free energy decomposition
Author(s) -
Zoete Vincent,
Meuwly Markus,
Karplus Martin
Publication year - 2005
Publication title -
proteins: structure, function, and bioinformatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.699
H-Index - 191
eISSN - 1097-0134
pISSN - 0887-3585
DOI - 10.1002/prot.20528
Subject(s) - monomer , dimer , chemistry , alanine , binding energy , residue (chemistry) , crystallography , computational chemistry , alanine scanning , decomposition , stereochemistry , atomic physics , organic chemistry , physics , biochemistry , polymer , amino acid , mutagenesis , mutation , gene
A calculation of the binding free energy for the dimerization of insulin has been performed using the molecular mechanics–generalized Born surface area approach. The calculated absolute binding free energy is −11.9 kcal/mol, in approximate agreement with the experimental value of −7.2 kcal/mol. The results show that the dimerization is mainly due to nonpolar interactions. The role of the hydrogen bonds between the 2 monomers appears to give the direction of the interactions. A per‐atom decomposition of the binding free energy has been performed to identify the residues contributing most to the self association free energy. Residues B24–B26 are found to make the largest favorable contributions to the dimerization. Other residues situated at the interface between the 2 monomers were found to make favorable but smaller contributions to the dimerization: Tyr B16, Val B12, and Pro B28, and to an even lesser extent, Gly B23. The energy decomposition on a per‐residue basis is in agreement with experimental alanine scanning data. The results obtained from a single trajectory (i.e., the dimer trajectory is also used for the monomer analysis) and 2 trajectories (i.e., separate trajectories are used for the monomer and dimer) are similar. Proteins 2005. © 2005 Wiley‐Liss, Inc.