| Autor: |
Molavi Tabrizi A; Department of Mechanical and Industrial Engineering, Northeastern University , Boston, Massachusetts 02115, United States., Goossens S; Department of Mechanical and Industrial Engineering, Northeastern University , Boston, Massachusetts 02115, United States., Mehdizadeh Rahimi A; Department of Mechanical and Industrial Engineering, Northeastern University , Boston, Massachusetts 02115, United States., Cooper CD; Departamento de Ingeniería Mecánica and Centro Científico Tecnológico de Valparaíso (CCTVal), Universidad Técnica Federico Santa María , Valparaiso, Chile., Knepley MG; Department of Computational and Applied Mathematics, Rice University , Houston, Texas 77005, United States., Bardhan JP; Department of Mechanical and Industrial Engineering, Northeastern University , Boston, Massachusetts 02115, United States. |
| Abstrakt: |
We extend the linearized Poisson-Boltzmann (LPB) continuum electrostatic model for molecular solvation to address charge-hydration asymmetry. Our new solvation-layer interface condition (SLIC)/LPB corrects for first-shell response by perturbing the traditional continuum-theory interface conditions at the protein-solvent and the Stern-layer interfaces. We also present a GPU-accelerated treecode implementation capable of simulating large proteins, and our results demonstrate that the new model exhibits significant accuracy improvements over traditional LPB models, while reducing the number of fitting parameters from dozens (atomic radii) to just five parameters, which have physical meanings related to first-shell water behavior at an uncharged interface. In particular, atom radii in the SLIC model are not optimized but uniformly scaled from their Lennard-Jones radii. Compared to explicit-solvent free-energy calculations of individual atoms in small molecules, SLIC/LPB is significantly more accurate than standard parametrizations (RMS error 0.55 kcal/mol for SLIC, compared to RMS error of 3.05 kcal/mol for standard LPB). On parametrizing the electrostatic model with a simple nonpolar component for total molecular solvation free energies, our model predicts octanol/water transfer free energies with an RMS error 1.07 kcal/mol. A more detailed assessment illustrates that standard continuum electrostatic models reproduce total charging free energies via a compensation of significant errors in atomic self-energies; this finding offers a window into improving the accuracy of Generalized-Born theories and other coarse-grained models. Most remarkably, the SLIC model also reproduces positive charging free energies for atoms in hydrophobic groups, whereas standard PB models are unable to generate positive charging free energies regardless of the parametrized radii. The GPU-accelerated solver is freely available online, as is a MATLAB implementation. |
