Improvements to the ABSINTH Force Field for Proteins Based on Experimentally Derived Amino Acid Specific Backbone Conformational Statistics.

We present an improved version of the ABSINTH implicit solvation model and force field paradigm (termed ABSINTH-C) by incorporating a grid-based term that bootstraps against experimentally derived and computationally optimized conformational statistics for blocked amino acids. These statistics provide high-resolution descriptions of the intrinsic backbone dihedral angle preferences for all 20 amino acids. The original ABSINTH model generates Ramachandran plots that are too shallow in terms of the basin structures and too permissive in terms of dihedral angle preferences. We bootstrap against the reference optimized landscapes and incorporate CMAP-like residue-specific terms that help us reproduce the intrinsic dihedral angle preferences of individual amino acids. These corrections that lead to ABSINTH-C are achieved by balancing the incorporation of the new residue-specific terms with the accuracies inherent to the original ABSINTH model. We demonstrate the robustness of ABSINTH-C through a series of examples to highlight the preservation of accuracies as well as examples that demonstrate the improvements. Our efforts show how the recent experimentally derived and computationally optimized coil-library landscapes can be used as a touchstone for quantifying errors and making improvements to molecular mechanics force fields.