I am a student in the Joint Carnegie Mellon - University of Pittsburgh Ph.D. Program in Computational Biology (CPCB).
I work for Prof. Ivet Bahar. My research primarily focuses on protein and small-molecule interactions and the role of intrinsic dynamics of proteins in small-molecule recognition and binding events. Particularly, I model protein-inhibitor interactions using flexible ligand/side-chain docking methods while accounting for protein flexibility using simplified elastic network models, such as Anisotropic Network Model (ANM). In , we showed that up to 80% structural variability observed in different inhibitor bound forms of popular drug target enzymes can be described by only a few collective modes describing intrinsic fluctuations of the target protein, as modelled using ANM. Our dataset included HIV-RT, p38 MAP kinase, and cyclin-dependent kinase 2. The implication of this study is that globular changes observed in different small-molecule bound structures of the same protein are, to a great extent, consequences of conformational selection. To support this view, we also showed that ANM predictions correlate with solution dynamics of ubiquitin and calmodulin.
On biological side of my work, I am interested in particularly dual-specificity phosphatases (DSPs) as drug targets. DSPs, such as MAP kinase phosphatases -1 and -3, and Cdc25B are implicated in cancer, but are challanging targets. There are a few DSP inhibitors which lack potency and selectivity. My interest is establishing a structural basis whereby known DSP inhibitors can be improved to be potent and selective towards serving as chemical probes in advancing the role of DSPs in human diseases. I had built a prototypical tool to analzye, visualize, and share my modelling. This link illustrates models for . These are active site inhibitors of MKP-1, and also closely related family member MKP-3. Previously, we discussed that . Recent discovery of an opened new avenues which can be exploited for designing novel, potent, and selective MKP inhibitors. My current focus is now on identifying compounds working in a similar mechanism and charaterization of allosteric binding sites.