A New Transfer Free Energy Based Implicit Solvation Model for the Description of Disordered and Folded Proteins

Most biological events occur on time scales that are
difficult
to access using conventional all-atom molecular dynamics simulations
in explicit solvent. Implicit solvent techniques offer a promising
solution to this problem, alleviating the computational cost associated
with the simulation of large systems and accelerating the sampling
compared to explicit solvent models. The substitution of water molecules
by a mean field, however, introduces simplifications that may penalize
accuracy and impede the prediction of certain physical properties.
We demonstrate that existing implicit solvent models developed using
a transfer free energy approach, while satisfactory at reproducing
the folding behavior of globular proteins, fare less well in characterizing
the conformational properties of intrinsically disordered proteins.
We develop a new implicit solvent model that maximizes the degree
of accuracy for both disordered and folded proteins. We show, by comparing
the simulation outputs to experimental data, that in combination with
the a99SB-disp force field, the implicit solvent model can describe
both disordered (aβ40, PaaA2, and drkN SH3) and folded ((AAQAA)3, CLN025, Trp-cage, and GTT) peptides. Our implicit solvent
model permits a computationally efficient investigation of proteins
containing both ordered and disordered regions, as well as the study
of the transition between ordered and disordered protein states.