**************** The 19th., Lab Seminar ****************************

Date: Thu, February 14, 2008 PM 2:30-

Place: No.616 Seminar room
             Graduate School of Information Science

Speaker: Yoshiyuki Koyano

Title: Comparison of Charge Models for Fixed-Charge Force Fields: 
Small-Molecule Hydration Free Energies in Explicit Solvent
D. L. Mobley, E. Dumont, J. D. Chodera and K. A. Dill, 
J. Phys. Chem. B, 111, 2242 (2007).

Abstract:
 In molecular simulations with fixed-charge force fields, the choice of 
partial atomic charges influences numerous computed physical properties, 
including binding free energies. Many molecular mechanics force fields 
specify how nonbonded parameters should be determined, but various choices 
are often available for how these charges are to be determined for arbitrary 
small molecules. Here, we compute hydration free energies for a set of 44 
small, neutral molecules in two different explicit water models (TIP3P and 
TIP4P-Ew) to examine the influence of charge model on agreement with experiment. 
Using the AMBER GAFF force field for nonbonded parameters, we test several 
different methods for obtaining partial atomic charges, including two fast 
methods exploiting semiempirical quantum calculations and methods deriving 
charges from the electrostatic potentials computed with several different 
levels of ab initio quantum calculations with and without a continuum 
reaction field treatment of solvent. We find that the best charge sets give 
a root-mean-square error from experiment of roughly 1 kcal/mol. Surprisingly, 
agreement with experimental hydration free energies does not increase
substantially with increasing level of quantum theory, even when the quantum 
calculations are performed with a reaction field treatment to better model 
the aqueous phase. We also find that the semiempirical AM1-BCC method for 
computing charges works almost as well as any of the more computationally 
expensive ab initio methods and that the root-mean-square error reported 
here is similar to that for implicit solvent models reported in the literature. 
Further, we find that the discrepancy with experimental hydration free energies
grows substantially with the polarity of the compound, as does its variation 
across theory levels.

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************* 平成19年度 第18回 長岡研 研究室セミナー *************

日　時： 2月14日（木） 14:30～

場　所： 情報科学研究科棟 ６階 ６１６号室
　　　 　（使用されている場合、６０３号室）

発表者：　小谷野　哲之
       　 yoshiyuki koyano

タイトル：(論文紹介) 
Comparison of Charge Models for Fixed-Charge Force Fields: 
Small-Molecule Hydration Free Energies in Explicit Solvent
D. L. Mobley, ?. Dumont, J. D. Chodera and K. A. Dill, 
J. Phys. Chem. B, 111, 2242 (2007).

　固定電荷の力場を用いた分子シミュレーションでは、部分原子電荷の選択方法が、
結合自由エネルギー等の多くの物理量の計算値に影響を与える。非結合パラメータ
の決定方法に応じて多くの分子力学的力場があるが、任意の小分子に対する電荷の
決定方法には様々な選択肢がある。異なる水モデル（TIP3PとTIP4P-Ew）で構成され
た液体水中の44種類の中性分子に対して、水和自由エネルギーの実験値との一致に
関して採用した電荷モデルが与える影響を調査した。非結合パラメータに対しては
AMBER GAFF力場を用いて、いくつかの部分原子電荷の決定方法を試した。半経験的
量子力学計算から電荷を求める方法と、非経験的計算による静電ポテンシャルから
電荷を求める方法である。後者については、溶媒の連続体反応場を利用した場合に
ついても行った。最も良い電荷の組み合わせでは、実験との根二乗平均誤差が約1 
kcal/molとなった。驚くべきことに、理論レベルを上げ、反応場で取り扱っても、
水和自由エネルギーの実験値との一致は、大きく向上しなかった。半経験的AM1-BCC
法の結果は他の計算コストの高い非経験的方法とほぼ同等だった。根二乗平均誤差
は誘電体溶媒モデルに対して得られた誤差と近いことが判った。すべての理論レベ
ルにおいて、実験との不一致は溶質の極性とともに増大することが判った。

 In molecular simulations with fixed-charge force fields, the choice of 
partial atomic charges influences numerous computed physical properties, 
including binding free energies. Many molecular mechanics force fields 
specify how nonbonded parameters should be determined, but various choices 
are often available for how these charges are to be determined for arbitrary 
small molecules. Here, we compute hydration free energies for a set of 44 
small, neutral molecules in two different explicit water models (TIP3P and 
TIP4P-Ew) to examine the influence of charge model on agreement with experiment. 
Using the AMBER GAFF force field for nonbonded parameters, we test several 
different methods for obtaining partial atomic charges, including two fast 
methods exploiting semiempirical quantum calculations and methods deriving 
charges from the electrostatic potentials computed with several different 
levels of ab initio quantum calculations with and without a continuum 
reaction field treatment of solvent. We find that the best charge sets give 
a root-mean-square error from experiment of roughly 1 kcal/mol. Surprisingly, 
agreement with experimental hydration free energies does not increase
substantially with increasing level of quantum theory, even when the quantum 
calculations are performed with a reaction field treatment to better model 
the aqueous phase. We also find that the semiempirical AM1-BCC method for 
computing charges works almost as well as any of the more computationally 
expensive ab initio methods and that the root-mean-square error reported 
here is similar to that for implicit solvent models reported in the literature. 
Further, we find that the discrepancy with experimental hydration free energies
grows substantially with the polarity of the compound, as does its variation 
across theory levels.

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