Class of 2005
sidc@jhu.edu | B.A. Neuroscience, Johns Hopkins University
Research
The structural characterization of protein-protein interactions can provide deep insight into their function. The enormous number of such interactions in the cell and difficulty of experimental methods in structure determination of complexes, there is a clear need for computational methods that predict protein complex structure (known as protein docking). These methods predict high-resolution structures of protein complexes from their unbound component structures. The need for backbone variability in docking arises from observed differences in backbone conformation between the unbound starting structure and the bound structure that confound most current docking methods. This is primarily due to two sources: 1) binding-induced conformation changes from the unbound state and 2 uncertainties in the structure of the unbound components. The former is present, to varying degrees, in the formation of all protein complexes. The latter is found when the unbound structure is determined using NMR or is the result of protein structure prediction using comparative modeling. In both cases, the more pronounced the differences in backbone conformation to the bound state, the more difficult a target it presents for docking. Adequate incorporation of conformational plasticity in docking can go far in both predicting protein complexes from unbound crystal structures, but also expand the list of achievable docking targets by using NMR structures and homology models. My research focuses on developing methods that incorporate backbone conformational plasticity in docking by modeling biophysical mechanisms of binding. We test these methods in the Critical Assessment of PRotein Interactions (CAPRI), a community-wide blind structure prediction project, and on an established benchmark of target complexes of varying difficulty.
Publications
Chaudhury, S. & Gray, J.J., (2008) Conformer selection and induced fit in flexible backbone protein-protein docking using computational and NMR ensembles. J. Mol. Biol. 381:1068-1087
Pickin, K., Chaudhury, S., Dancy B.C.R., Gray J.J., Cole, P.A. (2008) Analysis of protein kinase autophosphorylation using expressed protein ligation and computational modeling. J. Am. Chem. Soc. 130:5667-5869.
Chaudhury, S., A. Sircar, A. Sivasubramanian, M. Berrondo, and J.J. Gray. (2007) Incorporating biochemical information and backbone flexibility in RosettaDock for CAPRI rounds 6-12. Proteins 69:793-800.
Chaudhury, S., J.M. Eisinger, H. Lei, J. Hicks, and K.A. Turano. (2004) Visual illusion in far space alters women's walking in a virtual world. Exp. Brain Res. 159:360-369.
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