A revolutionary advance in modern force fields

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 latest version of the force field, OPLS4, builds upon the extensive coverage and high level of accuracy achieved in OPLS3e, by improving the accuracy of functional groups that have presented significant modeling challenges in the past. In particular, charged groups and sulfur containing moieties are  significantly improved with OPLS4. 

Discover how OPLS4 can improve the quality of computational predictions

Accurate parameters for proteins and nucleic acids
In addition to extensive coverage of small molecules, OPLS4 also contains improved parameters for proteins and nucleic acids, leading to marked improvement in structural stabilization during long MD simulations.

Improved conformational analyses
OPLS4’s more accurate description of torsional energies leads to improved conformational analyses, docking poses and binding free energies.

More accurate free energy predictions
OPLS4 produces accurate predictions of solvation free energies and binding free energies, 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 bonding, chalcogen bonding and lone pairs are particularly poorly represented by atomic partial charges. OPLS4 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 OPLS4, 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 to derive the missing parameters yourself.

OPLS4 Improvements
Building upon the success of OPLS3e, the OPLS4 force field brings further refinements and improvements including more accurate modeling of sulfur and charged groups. The respective advances lead to improved accuracy in FEP+ binding affinity predictions.

Citations and Acknowledgements

Schrödinger Release 2022-4: Schrödinger, LLC, New York, NY, 2021.

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