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Comparison of electrostatic potential around proteins calculated from Amber and AM1 charges: application to mutants of prion protein

Zuegg, Johannes; Bliznyuk, Andrei; Gready, Jill

Description

On the basis of arguments of complementary fit of shape and charge polarity or hydrophobicity, molecular electrostatic potentials (MEPs) around proteins are commonly used to deduce likely sites for interaction with ligands or other proteins, including for variations such as mutations. But protein MEPs calculated classically from fixed force field descriptions, including those with implicit solvent models such as in Delphi, do not allow for repolarization of protein residues within the protein...[Show more]

dc.contributor.authorZuegg, Johannes
dc.contributor.authorBliznyuk, Andrei
dc.contributor.authorGready, Jill
dc.date.accessioned2015-12-13T23:07:31Z
dc.date.available2015-12-13T23:07:31Z
dc.identifier.issn0026-8976
dc.identifier.urihttp://hdl.handle.net/1885/86242
dc.description.abstractOn the basis of arguments of complementary fit of shape and charge polarity or hydrophobicity, molecular electrostatic potentials (MEPs) around proteins are commonly used to deduce likely sites for interaction with ligands or other proteins, including for variations such as mutations. But protein MEPs calculated classically from fixed force field descriptions, including those with implicit solvent models such as in Delphi, do not allow for repolarization of protein residues within the protein system; hence, their representations are likely to be variably inaccurate. Linear-scaling methods now allow calculation of MEPs quantum mechanically for systems as large as proteins, and can account for polarization explicitly. Here we compare MEPs derived from AM1 charge distributions calculated by Mopac2000 with those from the classical Amber force field. Our models are mutants of prion protein (PrP), a protein with an unusually high number of charged residues. The results demonstrate that static point charges, as used in most current force fields, cannot reproduce the MEP of macromolecules. Also, it is not sufficient to account for the influence of nearby atoms connected by chemical bonds; the influence of nearby atoms in space is at least as important. Thus, further progress in the accuracy and wider applicability of force fields requires proper accounting for polarization. Mopac2000 calculations can provide the necessary data for checking new force fields and/or parameter fitting.
dc.publisherTaylor & Francis Group
dc.sourceMolecular Physics
dc.subjectKeywords: Chemical bonds; Electrostatics; Hydrophobicity; Macromolecules; Mathematical models; Numerical analysis; Molecular electrostatic potential; Mutants; Prion protein; Proteins
dc.titleComparison of electrostatic potential around proteins calculated from Amber and AM1 charges: application to mutants of prion protein
dc.typeJournal article
local.description.notesImported from ARIES
local.description.refereedYes
local.identifier.citationvolume101
dc.date.issued2003
local.identifier.absfor030799 - Theoretical and Computational Chemistry not elsewhere classified
local.identifier.absfor110106 - Medical Biochemistry: Proteins and Peptides (incl. Medical Proteomics)
local.identifier.ariespublicationMigratedxPub15053
local.type.statusPublished Version
local.contributor.affiliationZuegg, Johannes, Alchemia Pty Ltd
local.contributor.affiliationBliznyuk, Andrei, Administrative Division, ANU
local.contributor.affiliationGready, Jill, College of Medicine, Biology and Environment, ANU
local.bibliographicCitation.issue15
local.bibliographicCitation.startpage2437
local.bibliographicCitation.lastpage2450
dc.date.updated2015-12-12T08:09:22Z
local.identifier.scopusID2-s2.0-1542287461
CollectionsANU Research Publications

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