8070
J. Phys. Chem. B 1998, 102, 8070-8079
Application of the RESP Methodology in the Parametrization of Organic Solvents Thomas Fox† and Peter A. Kollman* Department of Pharmaceutical Chemistry, UniVersity of California, San Francisco, California 94143-0446 ReceiVed: May 30, 1997; In Final Form: July 23, 1998
We present parametrizations for the nonaqueous solvents dimethyl sulfoxide, ethanol, CCl4, CHCl3, and CH2Cl2 that are compatible with the recent AMBER force field by Cornell et al. (J. Am. Chem. Soc. 1995, 117, 5179-5197). With the general procedure for generating new parameters and the RESP approach to obtain the atomic charges, we achieve flexible all-atom solvent models whose density, heat of vaporization, diffusion constant, and rotational correlation times aresespecially for a generic force fieldsin good agreement with available experimental data.
1. Introduction To date, most MD simulations of organic and bioorganic molecules in solution reported in the literature employ some form of water model as the solvent. This is understandable as almost all naturally occurring biochemical processes and many laboratory experiments use aqueous media. However, organic solvents also provide a common medium for organic synthesis as well as physical organic investigations. An application where the use of an explicit solvent may be especially important is restrained molecular dynamics simulations using NMR data, which very often are obtained using CDCl3 or DMSO-d6 as the solvent. To perform computer simulations directed at modeling organic chemistry in solution, intermolecular potential functions have been developed for many organic solvents, including hydrocarbons,1-4 alcohols,5,6 ethers,5 DMSO,7-9 halomethanes,3,10-18 and acetonitrile.19,20 Recently, Jorgensen showed that his new OPLS all-atom force field is very well suited for the simulation of a wide variety of nonaqueous solvents.21 However, many of these available force fields for organic solvents have the disadvantage that they either assume a rigid solvent molecule or that a single interaction center is used for a carbon atom and the nonpolar hydrogens attached to it (unitedatom method). Additionally, it is not clear how compatible such solvent models are with the new AMBER force field by Cornell et al.,22 where experience shows that a good balance between solvent-solvent and solvent-solute interactions is essential for a good description of the system under investigation. An additional point is the trend to simulate more complicated systems, e.g., complex assemblies of polymers in solution, where the question of which is solute and which is solvent is ambiguous; therefore, a unified treatment of all particles in the system is desirable. One very important aspect of the Cornell et al. force field is a minimalistic and (at least in principle) algorithmic approach in the development of the parameters, which facilitates the extension to new functional groups and molecules. This easy, fast, and transferable derivation of force-field parameters should not only be possible for the solvated molecules, but for the surrounding solvent as well. Therefore, we decided to apply the protocol for the derivation of new parameters described by Cornell et al.22 to the develop† Present address: Boehringer Ingelheim Pharma KG, ACF/Computer Assisted Drug Discovery, 88397 Biberach/Riss, Germany.
ment of flexible all-atom models for some nonaqueous solvents. Caldwell et al.6 have derived parameters for methanol and N-methylacetamide using such a protocol. Here, we wish to extend this approach to a wider class of molecules. The parametrization of dimethyl sulfoxide (DMSO), ethanol, carbon tetrachloride (CCl4), chloroform (CHCl3), and methylene chloride (CH2Cl2) should also serve as an example of how to augment the Cornell et al. force field and test the claim of easy extendability. In addition, this effort can be used for further research on MD simulations in nonaqueous solvents.23,24 2. Methods Derivation of Parameters. In our simulation we used the AMBER force field by Cornell et al.22 which is based on the following functional form:
Vtotal )
∑
Kr(r - req)2 +
bonds
∑
Vn [1 + dihedrals 2 Aij Bij qiqj + (1) Rij12 Rij6 Rij
Kθ(θ - θeq)2 +
angles
cos(nφ - γ)] +
∑ i
