Coarse-Grained Potential Models for Phenyl-Based Molecules: I. Parametrization Using Experimental Data Russell DeVane,* ,† Michael L. Klein, † Chi-cheng Chiu, ‡ Steven O. Nielsen, ‡ Wataru Shinoda, § and Preston B. Moore ⊥ Institute for Computational Molecular Science and Department of Chemistry, Temple UniVersity, 1901 North 13th Street, Philadelphia, PennsylVania 19122, Department of Chemistry, The UniVersity of Texas at Dallas, 800 West Campbell Road, Richardson, Texas 75080, Research Institute for Computational Sciences, National Institute of AdVanced Industrial Science and Technology (AIST), Central 2, 1-1-1 Umezono, Tsukuba, Ibaraki 305-8568, Japan, and Department of Chemistry & Biochemistry, UniVersity of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PennsylVania 19104 ReceiVed: December 11, 2009; ReVised Manuscript ReceiVed: March 9, 2010 A coarse-grained intermolecular potential has been parametrized for phenyl-based molecules. The parametriza- tion was accomplished by fitting to experimental thermodynamic data. Specifically, the intermolecular potentials, which were based on Lennard-Jones functional forms, were parametrized and validated using experimental surface tension, density, and partitioning data. This approach has been used herein to develop parameters for coarse-grained interaction sites that are applicable to a variety of phenyl-based molecules, including analogues of the amino acid side chains of phenylalanine and tyrosine. Comparison of the resulting coarse-grain model to atomistic simulations shows a high level of structural and thermodynamic agreement between the two models, despite the fact that no atomistic simulation data was used in the parametrization of the coarse-grain intermolecular potentials. I. Introduction There is continuing interest in developing a coarse-grained (CG) potential for computational studies of soft matter and biological systems. CG models provide a means to expand the utility of existing computational resources by allowing the exploration of far greater temporal and spatial scales than is possible with traditional MD simulations utilizing full atomic (AA) detail. However, the added efficiency comes necessarily at a cost, namely, loss of resolution in the description of the system. Typically, several atoms comprise a single CG interac- tion site, thus reducing the number of interacting particles necessary to characterize the system. With this approach in mind, many groups have developed CG models using various ap- proaches with numerous applications appearing in the literature over the past four decades. 1-15 Herein, we present the application of a recently proposed methodology to develop CG MD models for phenyl-based molecules. This method is unique in that it removes the common dependence on AA MD simulations by making extensive use of experimental thermodynamic data. This approach builds on previous work by Nielsen et al., 16 which was extended and applied to the development of CG parameters for PEG surfac- tants and amino acids. 10-12,17 Phenyl-based molecules are of particular importance from a biological standpoint as they are constituents of proteins; for example, phenylalanine (PHE), tyrosine (TYR), and tryptophan (TRP) and are building blocks for other biologically important molecules. These molecules have been the focus of previous CG parametrization approaches. 9,18-24 The CG models and parametrization meth- odology presented herein are currently being employed for the development of CG models for a wide range of systems including lipids, amino acids, and charged surfactants. In our companion paper, we show how to adapt the present CG model to enable studies of fullerenes. 25 The methodology used for the parametrization and validation of the CG models will be presented in section II. The details of the parametrization will be presented in section III. In order to validate the model, comparison to AA MD and experimental data will be presented in section IV. Finally, the conclusions will be presented in section V. II. Methods A. Coarse Grain Model Potential. For generality and ease of implementation, the present CG model employs Lennard- Jones (LJ)-style nonbonded potential functions. This work and previous work has demonstrated the ability of these potentials to model systems at the CG level with sufficient accuracy to predict phase behavior and interfacial properties of surfactants. 10-12 For the models developed herein, the CG beads interact via a LJ 9-6 or LJ 12-4 potential given as follows The choice of prefactors for the LJ functions are selected such that V(σ) ) 0 and ǫ is the well depth. The choice of the LJ functional form (for example the LJ 9-6 in eq 1) is essentially an adjustable parameter used in the fitting procedure. We have previously explored various LJ styles including 6-4, 8-4, 10-4, 9-6, and 12-4. 10 For alkane interactions, the choice of * To whom correspondence should be addressed. † Temple University. ‡ The University of Texas at Dallas. § National Institute of Advanced Industrial Science and Technology (AIST). ⊥ University of the Sciences in Philadelphia. V(r) 9-6 ) 27 4 ǫ ( σ 9 r 9 - σ 6 r 6 ) V(r) 12-4 ) 3√ 3 2 ǫ ( σ 12 r 12 - σ 4 r 4 ) (1) J. Phys. Chem. B 2010, 114, 6386–6393 6386 10.1021/jp9117369  2010 American Chemical Society Published on Web 04/28/2010