OPLS3e: Extending Force Field Coverage for Drug-Like Small Molecules

J Chem Theory Comput. 2019 Mar 12;15(3):1863-1874. doi: 10.1021/acs.jctc.8b01026. Epub 2019 Mar 4.


Building upon the OPLS3 force field we report on an enhanced model, OPLS3e, that further extends its coverage of medicinally relevant chemical space by addressing limitations in chemotype transferability. OPLS3e accomplishes this by incorporating new parameter types that recognize moieties with greater chemical specificity and integrating an on-the-fly parametrization approach to the assignment of partial charges. As a consequence, OPLS3e leads to greater accuracy against performance benchmarks that assess small molecule conformational propensities, solvation, and protein-ligand binding.

MeSH terms

  • Amyloid Precursor Protein Secretases / chemistry
  • Amyloid Precursor Protein Secretases / metabolism
  • Aspartic Acid Endopeptidases / chemistry
  • Aspartic Acid Endopeptidases / metabolism
  • Humans
  • Ligands
  • Molecular Conformation
  • Molecular Docking Simulation*
  • Molecular Dynamics Simulation
  • Protein Binding
  • Proteins / chemistry
  • Proteins / metabolism*
  • Quantum Theory
  • Small Molecule Libraries / chemistry*
  • Small Molecule Libraries / pharmacology*
  • Thermodynamics*


  • Ligands
  • Proteins
  • Small Molecule Libraries
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human