title: Wetting of nonconserved residue-backbones: A feature indicative of aggregation associated regions of proteins.
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.
authors.affiliation: Biomolecular Modeling and Design Division, Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 138671, Singapore.|School of Computer Engineering, Nanyang Technological University, 639798, Singapore.
authors.forename: Mohan R
authors.initials: MR
authors.lastname: Pradhan
authors.affiliation: Biomolecular Modeling and Design Division, Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
authors.forename: Arumay
authors.initials: A
authors.lastname: Pal
authors.affiliation: Biomolecular Modeling and Design Division, Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
authors.forename: Zhongqiao
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Biomolecular Modeling and Design Division, Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 138671, Singapore.
authors.forename: Srinivasaraghavan
authors.initials: S
authors.lastname: Kannan
authors.affiliation: School of Computer Engineering, Nanyang Technological University, 639798, Singapore.
authors.forename: Kwoh
authors.initials: K
authors.lastname: Chee Keong
authors.affiliation: p53 Laboratory, A*STAR (Agency for Science, Technology and Research), 138648, Singapore.
authors.forename: David P
authors.initials: DP
authors.lastname: Lane
authors.affiliation: Biomolecular Modeling and Design Division, Bioinformatics Institute, A*STAR (Agency for Science, Technology and Research), 138671, Singapore.|Department of Biological Sciences, National University of Singapore, 117543, Singapore.|School of Biological Sciences, Nanyang Technological University, 637551, Singapore.
authors.forename: Chandra S
authors.initials: CS
authors.lastname: Verma
mesh_terms: D000595:Amino Acid Sequence; D001665:Binding Sites; D030562:Databases, Protein; D006860:Hydrogen Bonding; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D066329:Protein Aggregates; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D014867:Water / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D066329:Protein Aggregates; D011506:Proteins; D014867:Water
keywords: dehydrons; evolutionary conservation; protein aggregation; protein structure