Commun. Comput. Phys., 13 (2013), pp. 13-30.


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

Lin Wang 1, Zhe Zhang 1, Walter Rocchia 2, Emil Alexov 1*

1 Computational Biophysics and Bioinformatics, Department of Physics, Clemson University, Clemson, SC 29634, USA.
2 Drug Discovery and Development, Italian Institute of Technology, via Morego 30, 16163 Genova, Italy.

Received 30 June 2011; Accepted (in revised version) 12 September 2011
Available online 12 June 2012
doi:10.4208/cicp.300611.120911s

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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PACS: 82.20.Wt
Key words: DelPhi, protein electrostatics, dielectric constant, Poisson-Boltzmann equation, protein flexibility, energy calculations, single point mutations.

*Corresponding author.
Email: lwang3@clemson.edu (L. Wang), zz@clemson.edu (Z. Zhang), Walter.Rocchia@iit.it (W. Rocchia), ealexov@clemson.edu (E. Alexov)
 

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