A novel quantum chemical approach to the computation of the solvation free energy of a biological molecule with structural flexibility

Hideaki Takahashi, Yuichi Iwata, Ryohei Kishi, Masayoshi Nakano

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

We have recently developed a novel quantum chemical approach, referred to as QM/MM-ER, to compute quantum chemically the solvation free energy of a molecule in a solution. The point of our method is to combine the hybrid QM/MM (quantum mechanical/molecular mechanical) approach with a novel statistical theory of solutions termed as theory of energy representation. Within the framework of the QM/MM-ER approach, the solvation free energy of a solute is constructed in terms of the distribution functions between the solute and the solvent for the solution and the pure solvent systems. In this paper, we extend our method to a biological molecule with structural flexibility. The pilot system we choose is a small peptide chain Chignolin consisting of 10 amino acid residues immersed in water. The solvation free energy of the peptide chain has been evaluated as -230.8kcal/mol by QM/MM-ER. However, the energy distribution function for a solution system has non-zero values on such the lower energy coordinate that the distribution for the pure solvent completely vanishes, which gives rise to a loss of accuracy in the free energy calculation. We discuss the origin for such the unfavorable situation as well as the method to conquer the problem.

Original languageEnglish
Title of host publicationComputational Methods in Science and Engineering - Advances in Computational Science, Lectures Presented at the Int. Conference on Computational Methods in Science and Engineering 2008, ICCMSE 2008
Pages338-341
Number of pages4
DOIs
Publication statusPublished - 2009 Dec 1
Externally publishedYes
Event6th International Conference on Computational Methods in Sciences and Engineering 2008, ICCMSE 2008 - Hersonissos, Crete, Greece
Duration: 2008 Sep 252008 Sep 30

Publication series

NameAIP Conference Proceedings
Volume1148 2
ISSN (Print)0094-243X
ISSN (Electronic)1551-7616

Other

Other6th International Conference on Computational Methods in Sciences and Engineering 2008, ICCMSE 2008
CountryGreece
CityHersonissos, Crete
Period08/9/2508/9/30

Keywords

  • Free Energy
  • Kohn-Sham DFT
  • Peptide Chain
  • QM/MM-ER
  • Theory of Energy Representation

ASJC Scopus subject areas

  • Physics and Astronomy(all)

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    Takahashi, H., Iwata, Y., Kishi, R., & Nakano, M. (2009). A novel quantum chemical approach to the computation of the solvation free energy of a biological molecule with structural flexibility. In Computational Methods in Science and Engineering - Advances in Computational Science, Lectures Presented at the Int. Conference on Computational Methods in Science and Engineering 2008, ICCMSE 2008 (pp. 338-341). (AIP Conference Proceedings; Vol. 1148 2). https://doi.org/10.1063/1.3225309