Research Abstract:
Research in our lab is focused on three topics and these are as follows: 1) Mechanisms of protein aggregation and fibril formation: This is relevant for understanding the onset and progression of neurodegenerative disorders such as Huntington’s disease and Alzheimer’s disease. 2) Understanding how disordered proteins are involved in macromolecular recognition: The organization of regulatory networks hinges on the presence of hub proteins, which carry out their biological functions in direct contradiction of the classical structure-function paradigm. We are developing quantitative models and experimental probes to understand how protein disorder, i.e., a purported lack of well-defined 3-dimensional structure, is used to organize large-scale protein-protein and protein-nucleic acid interaction networks. 3) The design of tunable and responsive biomaterials: This is crucial for the delivery of therapeutic agents and for ultra-sensitivity in the detection of signals of cellular degeneration or the onset of tumors. We are involved in collaborations to design responsive peptide-based hydrogels for drug delivery. We are also developing a nanoinformatics resource that will be used by the National Cancer Institute for de novo redesign of nanotechnologies in cancer therapeutics and diagnostics. We currently receive funding from the National Science Foundation (NSF), the National Cancer Institute (NIH-NCI), and the National Institute for Neuronal Disorders and Stroke (NIH-NINDS).
Selected Publications:
Chen AA, Draper DE, Pappu RV. Molecular simulation studies of monovalent counterion-mediated interactions in a model RNA kissing loop. J. Mol. Biol. 2009. (In Press).
Vitalis A, Lyle N, Pappu RV. Thermodynamics of beta-sheet formation in polyglutamine. Biophys. J. 2009. (In Press).
Vitalis A, Pappu RV. ABSINTH: A new continuum solvation model for simulations of polypeptides in aqueous solutions. J. Comput. Chem. 2009 30: 673-700.
Vitalis A, Wang X, Pappu RV. Atomistic simulations of the effects of polyglutamine chain length and solvent quality on conformational equilibria and spontaneous homodimerization. J.Mol. Biol. 2008 384: 279-297.
Tran HT, Mao A, Pappu RV. Role of backbone-solvent interactions in determining conformational equilibria of intrinsically disordered polypeptides. J.Am. Chem. Soc. 2008 130: 7380-7392.
Last Updated: 06/22/2009 |