title: An accurate and efficient computation method of the hydration free energy of a large, complex molecule.
abstract: The hydration free energy (HFE) is a crucially important physical quantity to discuss various chemical processes in aqueous solutions. Although an explicit-solvent computation with molecular dynamics (MD) simulations is a preferable treatment of the HFE, huge computational load has been inevitable for large, complex solutes like proteins. In the present paper, we propose an efficient computation method for the HFE. In our method, the HFE is computed as a sum of 〈UUV〉/2 (〈UUV〉 is the ensemble average of the sum of pair interaction energy between solute and water molecule) and the water reorganization term mainly reflecting the excluded volume effect. Since 〈UUV〉 can readily be computed through a MD of the system composed of solute and water, an efficient computation of the latter term leads to a reduction of computational load. We demonstrate that the water reorganization term can quantitatively be calculated using the morphometric approach (MA) which expresses the term as the linear combinations of the four geometric measures of a solute and the corresponding coefficients determined with the energy representation (ER) method. Since the MA enables us to finish the computation of the solvent reorganization term in less than 0.1 s once the coefficients are determined, the use of the MA enables us to provide an efficient computation of the HFE even for large, complex solutes. Through the applications, we find that our method has almost the same quantitative performance as the ER method with substantial reduction of the computational load.
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Yoshidome
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Ekimoto
authors.affiliation: Division of Chemical Engineering, Graduate School of Engineering Science, Osaka University, Toyonaka, Osaka 560-8531, Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Matubayasi
authors.affiliation: Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 7-2-1 Kamino, Himeji-shi, Hyogo 670-8524, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Harano
authors.affiliation: Institute of Advanced Energy, Kyoto University, Uji, Kyoto 611-0011, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kinoshita
authors.affiliation: Graduate School of Medical Life Science, Yokohama City University, 1-7-29, Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Ikeguchi
mesh_terms: D003198:Computer Simulation; D016014:Linear Models; D008956:Models, Chemical; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry; D012996:Solutions / Q000737:chemistry; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics; D013997:Time Factors; D014867:Water / Q000737:chemistry*
chemical_list: D011506:Proteins; D012996:Solutions; D012997:Solvents; D014867:Water