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Nearest‐neighbor effects and structural preferences in dipeptides are a function of the electronic properties of amino acid side‐chains
Author(s) -
Dwyer Donard S.
Publication year - 2006
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.20906
Subject(s) - dipeptide , chemistry , side chain , substituent , amino acid , electronic structure , mulliken population analysis , protein secondary structure , peptide , peptide bond , stereochemistry , k nearest neighbors algorithm , protein structure , computational chemistry , crystallography , density functional theory , organic chemistry , biochemistry , polymer , artificial intelligence , computer science
The electronic properties of amino acid side‐chains are emerging as an important factor in the preference for secondary structure in proteins. These properties have not been fully characterized, nor has their role in the behavior of peptides been explored in any detail. The present studies sought to evaluate several possibilities: 1) that hydrophilicity can be expressed solely in electronic terms, 2) that substituent effects of side‐chains extend across the peptide bond, and (3) nearest‐neighbor effects in dipeptides correlate with secondary structural preferences. Quantum mechanics (QM) calculations were used to define the electronic properties of individual amino acids and dipeptides. It was found that the hydrophilicity of an amino acid side‐chain can be accurately represented as a function of the electron densities of its component atoms. In addition, the nature of an amino acid in the second position of a dipeptide affects the electronic properties (Mulliken populations and electron densities) of the main‐chain atoms of the first residue. Certain electronic features of the dipeptides strongly correlated with propensity for secondary structure. Specifically, Mulliken population data at the C α atom and N atom predicted preference for α‐helices versus coil and strand conformations, respectively. Analysis of dipeptides arrayed in either helical or extended structures revealed lengthening of main‐chain bonds in the α‐helical conformations. A thorough characterization of the electronic properties of amino acids and short peptide segments may provide a better understanding of the forces that determine secondary structure in proteins. Proteins 2006. © 2006 Wiley‐Liss, Inc.