title: Parameterization of the Hamiltonian Dielectric Solvent (HADES) Reaction-Field Method for the Solvation Free Energies of Amino Acid Side-Chain Analogs.
abstract: Optimization of the Hamiltonian dielectric solvent (HADES) method for biomolecular simulations in a dielectric continuum is presented with the goal of calculating accurate absolute solvation free energies while retaining the model's accuracy in predicting conformational free-energy differences. The solvation free energies of neutral and polar amino acid side-chain analogs calculated by using HADES, which may optionally include nonpolar contributions, were optimized against experimental data to reach a chemical accuracy of about 0.5 kcal mol(-1). The new parameters were evaluated for charged side-chain analogs. The HADES results were compared with explicit-solvent, generalized Born, Poisson-Boltzmann, and QM-based methods. The potentials of mean force (PMFs) between pairs of side-chain analogs obtained by using HADES and explicit-solvent simulations were used to evaluate the effects of the improved parameters optimized for solvation free energies on intermolecular potentials.
authors.affiliation: Theoretical Chemical Biology and Protein Modelling Group, Technische Universiät München (Germany).
authors.forename: Martin
authors.initials: M
authors.lastname: Zachmann
authors.affiliation: Lehrstuhl für Biomolekulare Optik, Ludwig-Maximilians Universität München (Germany). gerald.mathias@physik.uni-muenchen.de.
authors.forename: Gerald
authors.initials: G
authors.lastname: Mathias
authors.affiliation: Theoretical Chemical Biology and Protein Modelling Group, Technische Universiät München (Germany). antes@tum.de.
authors.forename: Iris
authors.initials: I
authors.lastname: Antes
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D003198:Computer Simulation; D012997:Solvents / Q000737:chemistry; D013816:Thermodynamics
chemical_list: D000596:Amino Acids; D012997:Solvents
keywords: continuum electrostatics; molecular dynamics; reaction field; solvation free energy; solvent effects