Improving the description of salt bridge strength and geometry in a Generalized Born model

The Generalized Born (GB) solvent model is widely used in molecular dynamics simulations because it can be less computationally expensive and it samples conformational changes more efficiently than explicit solvent simulations. Meanwhile, great efforts have been made in the past to improve its precision and accuracy. Previous studies have shown that reducing intrinsic GB radii of some hydrogen atoms would improve AMBER GB-HCT solvent model's accuracy on salt bridges. Here we present our finding that similar correction also shows dramatic improvement for the AMBER GB-OBC solvent model. Potential of mean force and cluster analysis for small peptide replica exchange molecular dynamics simulations suggested that new radii GB simulation with ff99SB/GB-OBC corrected salt bridge strength and achieved significantly higher geometry similarity with TIP3P simulation. Improved performance in 60 ns HIV-1 protease GB simulation further validated this approach for large systems.

Figure optionsDownload high-quality image (239 K)Download as PowerPoint slideResearch highlights▶ Reducing H radii improved salt bridge modeling in small-peptide GB simulation with ff99SB/GB-OBC. ▶ The same modification is further validated in HIV-1 protease system. ▶ PB method is also shown to benefit from radii modification.