title: QM/MM-Based Fitting of Atomic Polarizabilities for Use in Condensed-Phase Biomolecular Simulation.
abstract: Accounting for electronic polarization effects in biomolecular simulation (by using a polarizable force field) can increase the accuracy of simulation results. However, the use of gas-phase estimates of atomic polarizabilities αi usually leads to overpolarization in condensed-phase systems. In the current work, a combined QM/MM approach has been employed to obtain condensed-phase estimates of atomic polarizabilities for water and methanol (QM) solutes in the presence of (MM) solvents of different polarity. In a next step, the validity of the linear response and isotropy assumptions were evaluated based on the observed condensed-phase distributions of αi values. The observed anisotropy and low average values for the polarizability of methanol's carbon atom in polar solvents was explained in terms of strong solute-solvent interactions involving its adjacent hydroxyl group. Our QM/MM estimates for atomic polarizabilities were found to be close to values used in previously reported polarizable water and methanol models. Using our estimate for αO of methanol, a single set of polarizable force field parameters was obtained that is directly transferable between environments of different polarity.
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, VU University Amsterdam , De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
authors.forename: C Ruben
authors.initials: CR
authors.lastname: Vosmeer
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, VU University Amsterdam , De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
authors.forename: Ariën S
authors.initials: AS
authors.lastname: Rustenburg
authors.affiliation: IBM Almaden Research Center , 650 Harry Road, San Jose, California 95120, United States.
authors.forename: Julia E
authors.initials: JE
authors.lastname: Rice
authors.affiliation: IBM Almaden Research Center , 650 Harry Road, San Jose, California 95120, United States.
authors.forename: Hans W
authors.initials: HW
authors.lastname: Horn
authors.affiliation: IBM Almaden Research Center , 650 Harry Road, San Jose, California 95120, United States.
authors.forename: William C
authors.initials: WC
authors.lastname: Swope
authors.affiliation: Leiden/Amsterdam Center for Drug Research, Division of Molecular and Computational Toxicology, Department of Chemistry and Pharmaceutical Sciences, Faculty of Sciences, VU University Amsterdam , De Boelelaan 1083, 1081 HV Amsterdam, The Netherlands.
authors.forename: Daan P
authors.initials: DP
authors.lastname: Geerke