Insights into protein-DNA interactions from hydrogen bond energy-based comparative protein-ligand analyses.

Content Provider	Europe PMC
Author	Malik, Fareeha K. Guo, Jun‐tao
Abstract	AbstractHydrogen bonds play important roles in protein folding and protein–ligand interactions, particularly in specific protein–DNA recognition. However, the distributions of hydrogen bonds, especially hydrogen bond energy (HBE) in different types of protein–ligand complexes, is unknown. Here we performed a comparative analysis of hydrogen bonds among three non‐redundant datasets of protein–protein, protein–peptide, and protein–DNA complexes. Besides comparing the number of hydrogen bonds in terms of types and locations, we investigated the distributions of HBE. Our results indicate that while there is no significant difference of hydrogen bonds within protein chains among the three types of complexes, interfacial hydrogen bonds are significantly more prevalent in protein–DNA complexes. More importantly, the interfacial hydrogen bonds in protein–DNA complexes displayed a unique energy distribution of strong and weak hydrogen bonds whereas majority of the interfacial hydrogen bonds in protein–protein and protein–peptide complexes are of predominantly high strength with low energy. Moreover, there is a significant difference in the energy distributions of minor groove hydrogen bonds between protein–DNA complexes with different binding specificity. Highly specific protein–DNA complexes contain more strong hydrogen bonds in the minor groove than multi‐specific complexes, suggesting important role of minor groove in specific protein–DNA recognition. These results can help better understand protein–DNA interactions and have important implications in improving quality assessments of protein–DNA complex models.
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Page Count	12
ISSN	08873585
Journal	Proteins
Volume Number	90
DOI	10.1002/prot.26313
PubMed Central reference number	PMC9018545
Issue Number	6
PubMed reference number	35122321
e-ISSN	10970134
Language	English
Publisher	John Wiley & Sons, Inc.
Publisher Date	2022-02-14
Publisher Place	Hoboken, USA
Access Restriction	Open
Rights License	This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. © 2022 The Authors. Proteins: Structure, Function, and Bioinformatics published by Wiley Periodicals LLC.
Subject Keyword	binding specificity hydrogen bond energy minor groove protein–DNA protein–ligand
Content Type	Text
Resource Type	Article
Subject	Structural Biology Molecular Biology Biochemistry