Improved Poisson–Boltzmann Methods for High-Performance Computing

Abstract

Implicit solvent models based on the Poisson-Boltzmann equation (PBE) have been widely used to study electrostatic interactions in biophysical processes. These models often treat the solvent and solute regions as high and low dielectric continua, leading to a large jump in dielectrics across the molecular surface which is difficult to handle. Higher order interface schemes are often needed to seek higher accuracy for PBE applications. However, these methods are usually very liberal in the use of grid points nearby the molecular surface, making them difficult to use on high-performance computing platforms. Alternatively, the harmonic average (HA) method has been used to approximate dielectric interface conditions near the molecular surface with surprisingly good convergence and is well suited for high-performance computing. By adopting a 7-point stencil, the HA method is advantageous in generating simple 7-banded coefficient matrices, which greatly facilitate linear system solution with dense data parallelism, on high-performance computing platforms such as graphics processing unit (GPU). However, the HA method is limited due to its lower accuracy. Therefore, it would be of great interest for high-performance applications to develop more accurate methods while retaining the simplicity and effectiveness of the 7-point stencil discretization scheme. In this study, we have developed two new algorithms based on the spirit of the HA method by introducing more physical interface relations and imposing the discretized Poisson's equation to the second order, respectively. Our testing shows that, for typical biomolecules, the new methods significantly improve the numerical accuracy to that comparable to the second-order solvers, and with ~65% overall efficiency gain on widely available highperformance GPU platforms.

Molecular Basis for Polyketide Ketoreductase–Substrate Interactions

“…Furthermore, MMPBSA analysis was performed to complement the stability score analysis [ 21 , 22 , 23 , 24 , 25 ]. Among the three trajectories simulated for each KR-ligand complex, the total binding free energy, , non-electrostatic binding free energy, , and electrostatic binding free energy, , from the last 100 ns of the trajectory with the highest average , were used for MMPBSA t -test analysis, grouped by KR type.…”

“…MMPBSA calculations [ 21 , 22 , 23 , 24 , 25 ] were conducted on the last 100 ns of each MD trajectory (frame interval is 1 ns) using the MMPBSA.py module in AmberTools18 . The ionic strength was set at 0.100 M to reflect the sodium ions originally present in the simulations.…”

Machine-Learned Molecular Surface and Its Application to Implicit Solvent Simulations

“…For example, the widely used harmonic average methods in a class of such strategies widely used in biomolecular simulations. [62][63][64]…”

Understanding the impact of ZBTB18 missense variation on transcription factor function in neurodevelopment and disease

“…The emerging availability of GPU-capable approaches in bioinformatics (Taylor-Weiner et al, 2019) and molecular simulation (He et al, 2020;Lee et al, 2018;Phillips et al, 2020;Wei, Luo, Qiu, Luo, & Qi, 2019) software coupled with the rapid growth in GPU hardware capability (including the increasing availability of GPU clusters) are critical to support saturation screening investigations of missense variants and their DNA-binding properties using in silico approaches.…”