OPLS3e
A revolutionary advance in modern force fields
The Advantages of the OPLS3e Force Field
Having accurate force field parameters is at the heart of obtaining useful molecular structures and relative energies, and yet many current in silico programs employ force fields that are years, if not decades, old, and suffer from lack of sufficient coverage for many common molecular motifs.
The creation of OPLS3 included systematically generating torsional parameters previously missing from earlier versions of the force field. Since the project’s inception, tens of thousands of additional torsional parameters have been created through high-level QM calculations. The latest version of OPLS3, OPLS3e, has achieved unprecedented coverage - small molecule torsion parameter coverage has been expanded to 95% relative to MMFF's 6% coverage, and OPLS_2005's 26% coverage - for relevant chemical space while improving the accuracy of predicted energies.
Accurate parameters for proteins and nucleic acids:
Besides improving the torsional parameters of small molecules, OPLS3 also contains improved parameters for protein backbones and side chains, as well as for nucleic acids, leading to marked improvement in structural stabilization during long MD simulations.
Improved conformational analyses:
OPLS3’s more accurate description of the potential energy surface leads to not only improved conformational analyses, but also improved docking poses.
More accurate free energy predictions:
OPLS3 produces more accurate predictions of solvation free energies. OPLS3 also reduces the error in binding free energy predictions, leading to more accurate rank ordering among congeneric series of compounds.
Virtual sites:
A single atom-centered charge is often inadequate for describing the true electrostatic nature of a chemical environment. Halogen sigma holes and lone pairs are particularly poorly represented by atomic partial charges. OPLS3 uses off-centered partial charges, or “virtual sites” to provide a better description of the true electronic environment, leading to improved energetics and structures.
Force field builder:
Even with the significantly more comprehensive coverage of OPLS3, there may still be occasions where the molecular motif under study isn’t fully parameterized. The Force Field Builder allows you to easily set up QM calculations from which you can derive the missing parameters yourself.
OPLS3e Improvements
Building upon the success of OPLS3, the OPLS3e force field brings further refinements and improvements including a 3x expansion of torsion parameters to reduce parameter transferability errors and a more accurate treatment of charges for novel heterocyclic chemistries. The respective advances leads to improved accuracy in FEP+ binding affinity predictions.
Citations and Acknowledgements
Schrödinger Release 2020-4: Schrödinger, LLC, New York, NY, 2020.
ö Harder, E.; Damm, W.; Maple, J.; Wu, C.; Reboul, M.; Xiang, J.Y.; Wang, L.; Lupyan, D.; Dahlgren, M.K.; Knight, J.L.; Kaus, J.W.; Cerutti, D.; Krilov, G.; Jorgensen, W.L.; Abel, R.; and Friesner, R.A., "OPLS3: a force field providing broad coverage of drug-like small molecules and proteins," J. Chem. Theory Comput., 2016, 12, 281-296
