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

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

Year:    2013

Communications in Computational Physics, Vol. 13 (2013), Iss. 1 : pp. 13–30

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.

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Journal Article Details

Publisher Name:    Global Science Press

Language:    English

DOI:    https://doi.org/10.4208/cicp.300611.120911s

Communications in Computational Physics, Vol. 13 (2013), Iss. 1 : pp. 13–30

Published online:    2013-01

AMS Subject Headings:    Global Science Press

Copyright:    COPYRIGHT: © Global Science Press

Pages:    18

Keywords: