My research interests include understanding how proteins allosterically transduce signal. To this end, I am employing a variety of computational methods. In particular, I am interested in the activation dynamics of a biomedically important class of molecules, G protein-coupled receptors. These integral membrane proteins transduce signal across the cell membrane, but the allosteric mechanism of their activation is not fully understood. I am applying molecular dynamics simulations and elastic network models to track structural transitions associated with activation/deactivation of a model receptor, rhodopsin. I am also interested in the development of novel methods for tracking structural transitions and analyses that allow us to directly compare simulation data to experimental observables. Leveraging multiple time-scale models I hope to produce a better picture of the allosteric cascade that connects the ligand-binding pocket to the protein’s active site.
- Leioatts, N., Suresh, P., Romo, T. D., and Grossfield, A., "Structure-based simulations reveal concerted dynamics of GPCR activation", Proteins, 2014 (in press)
- Mnpotra, J.S., Qiao, Z., Cai, J., Lynch, D. L., Grossfield, A., Leioatts, N., Hurst, D. P., Pitman, M. C., Song, Z.-H., Reggio, P.H., "Structural basis of G protein-coupled receptor-Gi protein interaction: formation of the cannabinoid CB2 Receptor/Gi Protein Complex", J. Biol. Chem., 2014 (in press)
- Leioatts, N., Mertz, B., Martinez-Mayorga, K., Romo, T. D., Pitman, M. C., Feller, S. E., Grossfield, A., Brown, M. F., "Retinal ligand mobility explains internal hydration and reconciles active rhodopsin structures", Biochemistry, 2013, DOI: 10.1021/bi4013947 (pdf)
- Leioatts, N., and Grossfield, A., "Molecular dynamics simulations of membranes and membrane proteins", in Molecular modeling at the atomic scale - Methods and applications in quantitative biology, ed. Ruhong Zhou, Taylor and Francis, to be published in 2014
- Seckler, J. M., Leioatts, N., Miao, H., and Grossfield, A. "The interplay of structure and dynamics in the function of HIV-1 reverse transcriptase", Proteins: Struc. Func. Bioinf., 2013, 81, 1792-1801, (pdf)
- Leioatts, N., Romo, T. D., and Grossfield, A., "Elastic network models are robust to variations in formalism", J. Chem. Theor. Comput., 2012, DOI:10.1021/ct3000316, (pdf)