OPLS Force Fields

forcefield

The OPLS (Optimized Potentials for Liquid Simulations) force fields are used throughout Schrödinger software for molecular mechanics calculations, molecular dynamics simulations, and free energy perturbation (FEP+) calculations. A force field is a set of functions and parameters that model the potential energy of a chemical system and calculate the forces on each particle. Schrödinger offers several OPLS force field versions, each building on the previous generation with expanded chemical coverage and improved accuracy.

OPLS4

The OPLS4 force field extends the OPLS3e [63], OPLS3 [62] and OPLS_2005 force fields to cover a much wider range of chemical space with better accuracy. This force field can be customized by using the Force Field Builder - OPLS4/OPLS5 Panel.

In input and output files, the string OPLS4 is used to refer to the OPLS4 force field. Note that the OPLS4 force field is called S-OPLS in command-line applications.

When using this force field, please use the following citation:

  • OPLS4, Schrödinger, Inc., New York, NY, 2021

In addition, please also cite the following paper:

  • Lu, C.; Wu, C.; Ghoreishi, D.; Chen, W.; Wang, L.; Damm, W.; Ross, G. A.; Dahlgren, M. K.; Russell, E.; Von Bargen, C. D.; Abel, R.; Friesner. R. A.; Harder, E.; OPLS4: Improving Force Field Accuracy on Challenging Regimes of Chemical Space. J. Chem. Theory Comput.2021, 17, 4291. DOI: 10.1021/acs.jctc.1c00302

 

The OPLS4 force field improves on OPLS3e with better water solvation, revised van der Waals parameters for charged functional groups, and new virtual sites for sulfur-containing moieties. Virtual sites are off-atom-centered charges that improve the representation of anisotropic electrostatic features such as lone pairs, sigma holes, and halogen bonds. For more information, see OPLS Virtual Sites.

OPLS5

The OPLS5 force field offers improved accuracy compared to the OPLS4 force field, but shows slower performance. This force field can be customized by using the Force Field Builder - OPLS4/OPLS5 Panel.

In input and output files, the string OPLS5 is used to refer to the OPLS5 force field. Note that the OPLS5 force field is called SPFF in command-line applications.

When using this force field, please use the following citations:

  • OPLS5, Schrödinger, Inc., New York, NY, 2021

  • Damm, W.; Dajnowicz, S.; Ghoreishi, D.; Yu, Y.; Ganeshan, K.; Madin, O.; Rudshteyn, B.; Hu, R.; Wu, M.; Shang, Y.; Albanese, S.; Zou, Y.; Ye, M.; Johnson, Z. L.; Trzoss, M.; Rafi, S.; Kapilashrami, K.; Saleh, N.; Ghanakota, P.; Zhang, Y.; Sampson, J.; Chen, W.; Wang, L.; Dahlgren, M. K.; Russell, E.; Leffler, A. E.; Abel, R.; Friesner, R. A.; Harder, E. D. OPLS5: Addition of Polarizability and Improved Treatment of Metals. ChemRxiv, 2024. DOI: 10.26434/chemrxiv-2024-2svr7

The OPLS5 force field extends OPLS4 with explicit polarization through Drude oscillators and improved modeling of transition metal complexes through fluctuating charge transfer (FlucCT) and improved metal-ligand geometry terms. For more information, see OPLS Virtual Sites.

OPLS_2005

OPLS_2005 is an enhanced version of the OPLS_2001 all atom force field developed by Schrödinger to provide a larger coverage of organic functionality. While retaining the features of OPLS-AA and OPLS_2001, torsional parameters have been refit to reproduce the conformational energetics derived at a higher level of quantum theory; additional stretch, bend, and torsion parameters and charges have been fit to support additional organic functionality. A much larger data set was analyzed for validation of the force field. The parameters for proteins have been updated to the ones published more recently [53].

Note: The OPLS_2001 force field is now considered obsolete and is no longer available. The following information is retained for its connection with OPLS_2005:

OPLS_2001 (or OPLSAA), developed by Professor W. Jorgensen of Yale University, is probably the best available for condensed-phase simulations of peptides. All force-field equations are identical to those of authentic OPLSAA [17]. Schrödinger’s implementation has been validated by comparison to BOSS OPLSAA calculations for a wide variety of organic systems. Comparisons to ab initio calculations and experiment show that OPLS_2001 reproduces conformational energies well for systems for which it has been specifically parameterized. Especially good results can be expected for proteins. With the exception of improved charge, van der Waals and torsion parameters for sulfur in thiols and thiol ethers [18], all parameters are native OPLS_2001. The new thio parameters, which use appreciably smaller charges on sulfur and which have been validated in liquid-phase simulations on thiols and thiol ethers, significantly improve the conformational energetics of CYS and MET residues in proteins.