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A Statistical Survey on the Binding Constants of Covalently Bound Protein–Ligand Complexes
Author(s) -
Li Xun,
Liu Zhihai,
Li Yan,
Li Jie,
Li Jiajie,
Wang Renxiao
Publication year - 2010
Publication title -
molecular informatics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.481
H-Index - 68
eISSN - 1868-1751
pISSN - 1868-1743
DOI - 10.1002/minf.200900003
Subject(s) - covalent bond , non covalent interactions , chemistry , ligand (biochemistry) , molecule , crystallography , computational chemistry , stereochemistry , hydrogen bond , organic chemistry , receptor , biochemistry
We have conducted a statistical survey to compare the binding constants of covalently and noncovalently bound protein–ligand complexes as two groups. In our study, a total of 1602 complexes formed between various types of proteins and small‐molecule ligands were selected from the PDBbind database (version 2008), all of which had high‐resolution three‐dimensional structures and reliable experimentally measured binding constants. These complexes were further classified as 79 covalent complexes, 131 Zn‐containing complexes, and 1392 noncovalent complexes. Covalent complexes formed through reversible mechanisms are found to be associated with higher binding constants than noncovalent complexes. Two‐sample T ‐test indicates that the difference is statistically significant. The advantage, however, is only modest (<20 folds). The same trend is also observed on a set of covalent and noncovalent complexes formed by thrombin. Our results indicate that reversible covalent bonding formed between protein and ligand will not automatically lead to a much tighter binding in general. Thus, our survey does not provide any supporting evidence for Houk’s hypothesis which states that covalent bonding formed between enzyme and transition state accounts for the extraordinary proficiency of enzymes.