### 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 language | English |
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Title of host publication | 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 |

Pages | 338-341 |

Number of pages | 4 |

DOIs | |

Publication status | Published - 2009 Dec 1 |

Externally published | Yes |

Event | 6th International Conference on Computational Methods in Sciences and Engineering 2008, ICCMSE 2008 - Hersonissos, Crete, Greece Duration: 2008 Sep 25 → 2008 Sep 30 |

### Publication series

Name | AIP Conference Proceedings |
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Volume | 1148 2 |

ISSN (Print) | 0094-243X |

ISSN (Electronic) | 1551-7616 |

### Other

Other | 6th International Conference on Computational Methods in Sciences and Engineering 2008, ICCMSE 2008 |
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Country | Greece |

City | Hersonissos, Crete |

Period | 08/9/25 → 08/9/30 |

### 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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## Cite this

*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