title: Rapid Estimation of Catalytic Efficiency by Cumulative Atomic Multipole Moments: Application to Ketosteroid Isomerase Mutants.
abstract: We propose a simple atomic multipole electrostatic model to rapidly evaluate the effects of mutation on enzyme activity and test its performance on wild-type and mutant ketosteroid isomerase. The predictions of our atomic multipole model are similar to those obtained with symmetry-adapted perturbation theory at a fraction of the computational cost. We further show that this approach is relatively insensitive to the precise amino acid side chain conformation in mutants and may thus be useful in computational enzyme (re)design.
authors.affiliation: Advanced Materials Engineering and Modelling Group, Faculty of Chemistry, Wrocław University of Science and Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Wiktor
authors.initials: W
authors.lastname: Beker
authors.affiliation: School of Biochemistry, Biomedical Sciences Building, University Walk , Bristol BS8 1TD, United Kingdom.|BrisSynBio Synthetic Biology Research Centre, Life Sciences Building, Tyndall Avenue, University of Bristol , Bristol BS8 1TQ, United Kingdom.|Centre of Computational Chemistry, School of Chemistry, Cantock's Close, University of Bristol , Bristol BS8 1TS, United Kingdom.
authors.forename: Marc W
authors.initials: MW
authors.lastname: van der Kamp
authors.affiliation: BrisSynBio Synthetic Biology Research Centre, Life Sciences Building, Tyndall Avenue, University of Bristol , Bristol BS8 1TQ, United Kingdom.|Centre of Computational Chemistry, School of Chemistry, Cantock's Close, University of Bristol , Bristol BS8 1TS, United Kingdom.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Mulholland
authors.affiliation: Advanced Materials Engineering and Modelling Group, Faculty of Chemistry, Wrocław University of Science and Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: W Andrzej
authors.identifier: http://orcid.org/0000-0001-5081-8175
authors.initials: WA
authors.lastname: Sokalski
mesh_terms: D000735:Androstenedione / Q000737:chemistry / Q000378:metabolism; D055162:Biocatalysis; D020134:Catalytic Domain; D007536:Isomerism; D056004:Molecular Dynamics Simulation; D050505:Mutant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D055672:Static Electricity; D013251:Steroid Isomerases / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D013816:Thermodynamics
chemical_list: D050505:Mutant Proteins; D000735:Androstenedione; D013251:Steroid Isomerases