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Wetting of nonconserved residue‐backbones: A feature indicative of aggregation associated regions of proteins
Author(s) -
Pradhan Mohan R.,
Pal Arumay,
Hu Zhongqiao,
Kannan Srinivasaraghavan,
Chee Keong Kwoh,
Lane David P.,
Verma Chandra S.
Publication year - 2016
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.24976
Subject(s) - chemistry , residue (chemistry) , protein aggregation , hydrogen bond , biophysics , conserved sequence , protein structure , molecule , biochemistry , peptide sequence , biology , organic chemistry , gene
Aggregation is an irreversible form of protein complexation and often toxic to cells. The process entails partial or major unfolding that is largely driven by hydration. We model the role of hydration in aggregation using “Dehydrons.” “Dehydrons” are unsatisfied backbone hydrogen bonds in proteins that seek shielding from water molecules by associating with ligands or proteins. We find that the residues at aggregation interfaces have hydrated backbones, and in contrast to other forms of protein–protein interactions, are under less evolutionary pressure to be conserved. Combining evolutionary conservation of residues and extent of backbone hydration allows us to distinguish regions on proteins associated with aggregation (non‐conserved dehydron‐residues) from other interaction interfaces (conserved dehydron‐residues). This novel feature can complement the existing strategies used to investigate protein aggregation/complexation. Proteins 2016; 84:254–266. © 2015 Wiley Periodicals, Inc.