Recently Jorgensen group has designed OPLS-AA/M force field for proteins and implemented it in NAMD, MCPRO programs. This study summarizes the key lessons learnt during the implementation of OPLS-AA/M force field in Gromacs, one of the most widely used molecular simulation packages.
This work has been done as part of LigParGen webserver. If you use this implementation, please cite the following references.
• Improved Peptide and Protein Torsional Energetics with the OPLS-AA Force Field Michael J. Robertson, Julian Tirado-Rives, and William L. Jorgensen J. Chem. Theory Comput., 2015, 11 (7), pp 3499–3509
• LigParGen web server: an automatic OPLS-AA parameter generator for organic ligands. Leela S. Dodda, Israel Cabeza de Vaca, Julian Tirado-Rives, and William L. Jorgensen Nucleic Acids Research, 2017, 45 (W1), pp W331–W336
Gromacs package has an existing implementation of OPLS-AA protein force field (FF) called OPLS-AA/L FF, but its implementation is not straightforward to understand because of the many define statements that override the dihedral and improper parameters. Unlike in CHARMM27 FF where a unique atom type is assigned for each of the protein atom, OPLS-AA/L uses OPLS-AA atom types but not torsions and impropers. This makes it tough for anyone to implement a modification of OPLS-AA/M protein FF without disturbing the existing OPLS-AA implementation. To overcome this problem, the strategy used for CHARMM27 FF has been studied, and it was observed that the simplicity of implementation lies in assigning unique atom types for biomolecules and adding the corresponding bonded and non-bonded parameters. This led to the conclusion that in order for implementing OPLS-AA/M FF in GMX, one needs to do the following modifications in existing OPLS-AA/L implementation.
|Gromacs Parameters||NAMD Parameters||Gromacs Function type|
|Bond force constant||
|Angle force constant||
To compare the implementations of NAMD and Gromacs, potential energies and its bonding and non-bonding components are compared for 23 AYA and 21 YYY tripeptides where Y is different amino acids. Tripeptides were created using pmx script was used. Thus, created peptides are prepared with VMD autopsf and optimized with NAMD. A single point energy calculation of the optimized structure was performed with Gromacs and the differences in energies were compared in Figure 1 below. From the comparison one can see that OPLS-AAM Gromacs implementation matches perfectly with NAMD implementation with an maximum difference in total energy of 0.01 kcal/mol.