OPLS force fields

W L. Jorgensen, OPLS force fields, in 77ie Encydopedia of Computational Chemistry, Vol. 3, P. v. R. Schleyer,... 

United Atom force fieldsare used often for biological polymers. In th esc m oleciiles, a reduced ii nm ber of explicit h ydrogen s can have a notable effect on the speed of the calculation. Both the BlOn and OPLS force fields are United Atom force fields. AMBER con tain s both aU nited and an All Atom force field. 

OPTS (Optim i/.ed Potentials for Liquid Simulations) is based on a force field developed by the research group of Bill Jorgensen now at Yale University and previously at Purdue University. Like AMBER, the OPLS force field is designed for calculations on proteins an d nucleic acids. It in troduces non bonded in leraclion parameters that have been carefully developed from extensive Monte Carlo liquid sim u lation s of small molecules. These n on-bonded interactions have been added to the bonding interactions of AMBER to produce a new force field that is expected to be better than AMBER at describing simulations w here the solvent isexplic-... 

I tie Hypci Cticm OPI.S force field gives results equivalent to the original OPLS force field. 

The OPLS force field is described in twtt papers, one discussing parameters for proteins W. L. Jorgensen and J. Tirado-Rives,/. Amer. (. hem. Soc., 110, 1557 (iy8K) and on e discii ssin g param eters for n iicleotide bases [J. Pranata, S. Wiersch ke, and W. L. Jorgen sen. , /.. Amer. Chem. Soc.. 117, 281(1 ( 1991)1. The force field uses the united atom concept ftir many, but not all. hydrttgens attached to carbons to allow faster calculation s on macromolecular systems. The amino and nucleic acid residue templates in HyperChein automatically switch to a united atom representation where appropriate when th e OPLS option is selected. 

A. rather complex procedure is used to determine the Born radii a values of which. calculated for each atom in the molecule that carries a charge or a partial charge. T Born radius of an afom (more correctly considered to be an effective Born radii corresponds to the radius that would return the electrostatic energy of the system accordi to the Bom equation if all other atoms in the molecule were uncharged (i.e. if the other ato only acted to define the dielectric boundary between the solute and the solvent). In Sti force field implementation, atomic radii from the OPLS force field are assigned to ec... 

In order for this to work, the force field must be designed to describe inter-molecular forces and vibrations away from equilibrium. If the purpose of the simulation is to search conformation space, a force field designed for geometry optimization is often used. For simulating bulk systems, it is more common to use a force field that has been designed for this purpose, such as the GROMOS or OPLS force fields. 

Significant progress in the optimization of VDW parameters was associated with the development of the OPLS force field [53]. In those efforts the approach of using Monte Carlo calculations on pure solvents to compute heats of vaporization and molecular volumes and then using that information to refine the VDW parameters was first developed and applied. Subsequently, developers of other force fields have used this same approach for optimization of biomolecular force fields [20,21]. Van der Waals parameters may also be optimized based on calculated heats of sublimation of crystals [68], as has been done for the optimization of some of the VDW parameters in the nucleic acid bases [18]. Alternative approaches to optimizing VDW parameters have been based primarily on the use of QM data. Quantum mechanical data contains detailed information on the electron distribution around a molecule, which, in principle, should be useful for the optimization of VDW... 

OPLS force field Monte Carlo simulation NB = Non-bonded cutoff distance in A... 

W. L. Jorgensen and J. Tirado-Rives, The OPLS force field for proteins. Energy... 

A significant issue widi modem force fields is that it can be difficult to simultaneously address both generality and suitability for use in condensed-phase simulations. For example, the MMFF94 force field is reasonably robust for gas-phase conformational analysis over a broad range of chemical functional groups, but erroneously fails to predict a periodic box of n-butane to be a liquid at —0.5 °C (Kaminski and Jorgensen 1996). The OPLS force field, on the other hand, is very accurate for condensed-phase simulations of molecules over which it is defined, but it is an example of a force field whose parameterization is limited primarily to functionality of particular relevance to biomolecules, so it is not obvious how to include arbitrary solutes in the modeling endeavor. 

Kaminski and Jorgensen (1998) have proposed one particularly simple QM/MM approach to address this problem, which tliey refer to as AMl/OPLS/CMl (AOC). In AOC, Monte Carlo calculations are canied out for solute molecules represented by the AMI Hamiltonian embedded in periodic boxes of solvent molecules represented by the OPLS force field. Thus, 7/qm in Eq. (13.1) is simply the AMI energy for the solute, and //mm is evaluated for all solvent-solvent interactions using the OPLS force field. The QM/MM interaction energy is computed in a fashion closely resembling the standard approach for MM non-bonded interactions... 

Tel. 212-280-2577, e-mail sl model%cuchem.bitnet A user-friendly molecular modeling package for molecular mechanics and conformational searching of organic molecules, proteins, nucleic acids, and carbohydrates. AMBER-, MM2-, and MM3-like and OPLS force fields implicit solvation model. Reads Cambridge and Brookhaven PDB files. VAX, Convex, Alliant, Cray, and workstations. 

Sequence analysis and biomolecular modeling. PRO-SIMULATE for molecular simulations with GROMOS, AMBER, and OPLS force fields. PROQUANTUM for semiempirical (MOPAC) and ab initio (CADPAC) calculations via a graphical interface. 

Jorgensen has parameterized by fitting properties of bulk liquids to Monte Carlo simulations to give the AMBER/OPLS force field (26,157, 158). Conceptually, one is attracted ly the use of liquids and their observable properties as constraints during the derivation of a force field that is destined to study the properties of solvated molecules. 

It is beyond the scope of this short review to list every available molecular mechanics program. Only a selected few programs are mentioned here, without descriptive details of the potential functions, minimization algorithms, or comparative evaluations. Both the CHARMM and AMBER force fields use harmonic potential functions to calculate protein structures. They were developed in the laboratories of Karplus and Kollman, respectively, and work remarkably well. The CFF and force fields use more complex potential functions. Both force fields were developed in commercial settings and based extensively or exclusively on results obtained from quantum mechanics. Unlike the other molecular mechanics methods, the OPLS force field was parameterized by Jorgensen to simulate solution phase phenomena. 

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