Robustness in the fitting of molecular mechanics parameters.

ABSTRACT: Automated methods for force field parametrization have attracted renewed interest of the community, but the robustness issues associated with the often ill-conditioned nature of parameter optimization have been vastly underappreciated in the recent literature. For this reason, this article offers a detailed description of the origin and nature of these issues. This includes a discussion of the restrained electrostatic potential fit (RESP) charge model, which does contain explicit robustness-enhancing measures albeit not in the context of bonded parameters, and which forms an inspiration for the present work. It is also discussed how all the bonded parameters in a Class I force field can be simultaneously fit using the linear least squares (LLS) procedure, and a novel restraining strategy i

SUBMITTER: Vanommeslaeghe K 

PROVIDER: S-EPMC4412823 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature