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.