Research involves computational and theoretical studies of biological, pharmaceutical and chemical systems. Specific areas of interest include structure-function relationships of proteins, carbohydrates and nucleic acids; computer-aided drug design targeting cancer, opioids and immunosuppression, among others, and the development of empirical force fields for biological and pharmaceutical compounds. These studies are performed in close collaboration with experimentalists allowing for a more detailed interpretation of experimental data while simultaneously leading to the refinement and development of novel theoretical approaches. Methods used include molecular modeling based on ab initio, semi-empirical, and empirical force field calculations, including molecular dynamics simulations, free energy perturbation calculations, macroscopic continuum dielectric calculations, database searching via docking approaches, and quantitative structure-activity relationships (QSAR). Empirical force field development is done in conjunction with the CHARMM molecule modelling program and novel CADD methodologies developed by MacKerell and co-workers include the Comformationally-Sampled Pharmacophore (CSP) and Site Identification by Ligand Competitive Saturation (SILCS) approaches.