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CH/π hydrogen bonds determine the selectivity of the Src homology 2 domain to tyrosine phosphotyrosyl peptides: An ab initio fragment molecular orbital study
Author(s) -
Ozawa Tomonaga,
Okazaki Kosuke
Publication year - 2008
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/jcc.20998
Subject(s) - fragment molecular orbital , hydrogen bond , ab initio , chemistry , tyrosine , fragment (logic) , proto oncogene tyrosine protein kinase src , natural bond orbital , molecular orbital , stereochemistry , computational chemistry , molecule , biochemistry , density functional theory , phosphorylation , organic chemistry , mathematics , algorithm
The CH/π hydrogen bond is a weak molecular force occurring between CH groups (soft acids) and π‐systems (soft bases), and has been recognized to be important in the interaction of proteins with their specific ligands. For instance, it is well known that Src homology‐2 protein (SH2) recognizes its specific pTyr peptide in two key regions, pTyr‐binding region and specificity‐determining region, by the use of attractive molecular forces, including the CH/π hydrogen bond. We hypothesized that the CH/π hydrogen bond plays a key role in determining the selectivity of SH2 proteins, and studied this issue by the ab initio fragment molecular orbital (FMO) method. The FMO calculations were carried out, at the HF/6‐31G* and MP2/6‐31G* level, for SH2 domains of Src, Grb2, P85α(N), Syk, and SAP, in complex with corresponding pTyr peptides. CH/π hydrogen bonds have in fact been found to be important in stabilizing the structure of the complexes. We conclude that the CH/π hydrogen bond plays an indispensable role in the recognition of SH2 domains with their specific pTyr peptides, thus playing a vital role in the signal transduction system. © 2008 Wiley Periodicals, Inc. J Comput Chem 2008