The Phase I effort successfully developed a fast boundary element method (BEM) to solve the linear Poisson-Boltzmann equation (PBE) for biomolecules immersed in ionic solution. Unlike previous fast BEMs which were limited to the Poisson equation (corresponding to zero ionic strength), the new BEM accommodates ionic strength effects and thus represents a major advance in biomolecular modeling. Problems involving up to 80,000 boundary elements were successfully carried out upon readily accessibly workstations. In Phase II, this new capability will be extended to solve the nonlinear PBE, efficiently couple the PBE solutions to molecular dynamics (MD) codes and model multiple molecules in relative motion. Modeling enhancements designed to further improve accuracy and reduce computational requirements will also be incorporated, including a novel local correction method for close surface-charge interactions. The fast parallel BEM analysis developed in Phase II will be extended to accommodate these new capabilities. To promote strong commercialization prospects, the input/output will be configured to interface with existing MD and molecular surface generation codes. The fast BEM PBE solver will be applied to large-scale biomolecular systems that have been previous inaccessible with emphasis upon advancing basic biological research and demonstrating the modeling capabilities of the fast nonlinear PBE analysis.
Successful completion of the Phase II effort will result in new powerful computational tools to address an enormous range of applications governed by the linear/nonlinear Poisson/Poisson/Boltzmann PDEs. The resulting software tools will allow researchers in government, academia and industry to carry out accurate electrostatic modeling studies of the large-scale biological systems on workstations or PCs. The knowledge gained from such studies will be valuable to the pharmaceutical and biomedical community.
| Boschitsch, Alexander H; Fenley, Marcia O (2011) A Fast and Robust Poisson-Boltzmann Solver Based on Adaptive Cartesian Grids. J Chem Theory Comput 7:1524-1540 |
| Boschitsch, Alexander H; Fenley, Marcia O (2004) Hybrid boundary element and finite difference method for solving the nonlinear Poisson-Boltzmann equation. J Comput Chem 25:935-55 |
