A new set of atomic radii for accurate estimation of solvation free energy by Poisson-Boltzmann solvent model.
Bottom Line: The presented PB radii were optimized using results from explicit solvent simulations of the large systems.The performances using our PB radii showed high accuracy for the estimation of solvation free energies at the level of the molecular fragment.The obtained PB radii are effective for the detailed analysis of the solvation effects of biomolecules.
Affiliation: Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, 5-15 Kashiwanoha, Kashiwa, Chiba, 277-8561, Japan; Laboratory for Computational Molecular Design, Quantitative Biology Center (QBiC), RIKEN, 1-6-5 Minatojima-Minatomachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.Show MeSH
Mentions: We used the thermodynamic integration (TI) method53 to calculate the polar component of the solvation free energy of the solute using TIP3P water.2 The polar solvation free energy ΔGpol is represented as: (3)where ΔGchg,wat and ΔGchg,vac are the charging free energy of the solute in water and in vacuo, respectively. Each charging free energy was calculated using the TI method based on the 15 λ-point Gaussian quadrature. Initial structures were set up by locating the solute at the center of a sphere of TIP3P water. The radii of the solvent spheres for the training molecules and for the test molecules were 45 Å and 53 Å, respectively; they are sufficiently large for the calculation of the solvation free energy. Our free energy calculation consists of two separate steps. The first step is the conventional MD simulation for conformational sampling. At each λ point, we performed 500 ps MD for the equilibration and another 500 ps MD for the production. No cut-off scheme was employed for the conformational sampling by MD simulations. Snapshots were sampled every 20 fs in the production run, and a total of 25,000 snapshots were saved at every λ point. The Langevin thermostat54 was used to maintain the temperature of the system at 300 K. All solute atoms were harmonically restrained at their initial positions with a force constant of 50 kcal mol−1 Å−1. The second step is to perform the TI method using the MD trajectories obtained from the first step for the calculation of the solvation free energy. In this step, we applied a cut-off scheme for long-range interactions to remove the artificial influence from water molecules near the boundary. Because the free energy calculated using a given cut-off distance is largely fluctuated (Fig. 1), we adopted the average of the solvation free energies using multiple cut-off distances. The cut-off distances ranged from 22 to 30 Å and 28 to 36 Å for the training molecules and test molecules, respectively, with a step size of 0.1 Å. The dynamics of the water molecules in these ranges fully corresponded to those of bulk water molecules.
Affiliation: Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, 5-15 Kashiwanoha, Kashiwa, Chiba, 277-8561, Japan; Laboratory for Computational Molecular Design, Quantitative Biology Center (QBiC), RIKEN, 1-6-5 Minatojima-Minatomachi, Chuo-ku, Kobe, Hyogo, 650-0047, Japan.