OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space

We
report on the development and validation of the OPLS4 force
field. OPLS4 builds upon our previous work with OPLS3e to improve
model accuracy on challenging regimes of drug-like chemical space
that includes molecular ions and sulfur-containing moieties. A novel
parametrization strategy for charged species, which can be extended
to other systems, is introduced. OPLS4 leads to improved accuracy
on benchmarks that assess small-molecule solvation and protein–ligand
binding.