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Using DelPhi Capabilities to Mimic Protein’s Conformational Reorganization with Amino Acid Specific Dielectric Constants

Published online by Cambridge University Press:  03 June 2015

Lin Wang ,
Zhe Zhang ,
Walter Rocchia  and
Emil Alexov
Lin Wang*
Affiliation:
Computational Biophysics and Bioinformatics, Department of Physics, Clemson University, Clemson, SC 29634, USA
Zhe Zhang*
Affiliation:
Computational Biophysics and Bioinformatics, Department of Physics, Clemson University, Clemson, SC 29634, USA
Walter Rocchia*
Affiliation:
Drug Discovery and Development, Italian Institute of Technology, via Morego 30, 16163 Genova, Italy
Emil Alexov*
Affiliation:
Computational Biophysics and Bioinformatics, Department of Physics, Clemson University, Clemson, SC 29634, USA
*
Email:lwang3@clemson.edu
Email:zz@clemson.edu
Email:Walter.Rocchia@iit.it
Corresponding author.Email:ealexov@clemson.edu
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Abstract

Many molecular events are associated with small or large conformational changes occurring in the corresponding proteins. Modeling such changes is a challenge and requires significant amount of computing time. From point of view of electrostatics, these changes can be viewed as a reorganization of local charges and dipoles in response to the changes of the electrostatic field, if the cause is insertion or deletion of a charged amino acid. Here we report a large scale investigation of modeling the changes of the folding energy due to single mutations involving charged group. This allows the changes of the folding energy to be considered mostly electrostatics in origin and to be calculated with DelPhi assigning residue-specific value of the internal dielectric constant of protein. The predicted energy changes are benchmarked against experimentally measured changes of the folding energy on a set of 257 single mutations. The best fit between experimental values and predicted changes is used to find out the effective value of the internal dielectric constant for each type of amino acid. The predicted folding free energy changes with the optimal, amino acid specific, dielectric constants are within RMSD=0.86 kcal/mol from experimentally measured changes.

Keywords

82.20.WtDelPhiprotein electrostaticsdielectric constantPoisson-Boltzmann equationprotein flexibilityenergy calculationssingle point mutations
Type
Research Article
Information
Communications in Computational Physics , Volume 13 , Issue 1 , January 2013 , pp. 13 - 30
Copyright
Copyright © Global Science Press Limited 2013

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