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Proteins. 2016 Feb;84(2):254-66. doi: 10.1002/prot.24976. Epub 2016 Jan 7.

Wetting of nonconserved residue-backbones: A feature indicative of aggregation associated regions of proteins.

Author information

1
Biomolecular Modeling and Design Division, Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
2
School of Computer Engineering, Nanyang Technological University, 639798, Singapore.
3
p53 Laboratory, A*STAR (Agency for Science, Technology and Research), 138648, Singapore.
4
Department of Biological Sciences, National University of Singapore, 117543, Singapore.
5
School of Biological Sciences, Nanyang Technological University, 637551, Singapore.

Abstract

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.

KEYWORDS:

dehydrons; evolutionary conservation; protein aggregation; protein structure

PMID:
26677132
DOI:
10.1002/prot.24976
[Indexed for MEDLINE]

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