Sidhartha Chaudhury

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SUMMARY PyRosetta is a stand-alone Python-based implementation of the Rosetta molecular modeling package that allows users to write custom structure prediction and design algorithms using the major Rosetta sampling and scoring functions. PyRosetta contains Python bindings to libraries that define Rosetta functions including those for accessing and(More)
RosettaDock has been increasingly used in protein docking and design strategies in order to predict the structure of protein-protein interfaces. Here we test capabilities of RosettaDock 3.2, part of the newly developed Rosetta v3.2 modeling suite, against Docking Benchmark 3.0, and compare it with RosettaDock v2.3, the latest version of the previous Rosetta(More)
As novel and drug-resistant bacterial strains continue to present an emerging health threat, the development of new antibacterial agents is critical. This includes making improvements to existing antibacterial scaffolds as well as identifying novel ones. The aim of this study is to apply a Bayesian classification QSAR approach to rapidly screen chemical(More)
High-resolution homology models are useful in structure-based protein engineering applications, especially when a crystallographic structure is unavailable. Here, we report the development and implementation of RosettaAntibody, a protocol for homology modeling of antibody variable regions. The protocol combines comparative modeling of canonical(More)
Polyvalent vaccines use a mixture of Ags representing distinct pathogen strains to induce an immune response that is cross-reactive and protective. However, such approaches often have mixed results, and it is unclear how polyvalency alters the fine specificity of the Ab response and what those consequences might be for protection. In this article, we(More)
Drug-resistant mutations (DRMs) in HIV-1 protease are a major challenge to antiretroviral therapy. Protease-substrate interactions that are determined to be critical for native selectivity could serve as robust targets for drug design that are immune to DRMs. In order to identify the structural mechanisms of selectivity, we developed a peptide-docking(More)
In CAPRI rounds 6-12, RosettaDock successfully predicted 2 of 5 unbound-unbound targets to medium accuracy. Improvement over the previous method was achieved with computational mutagenesis to select decoys that match the energetics of experimentally determined hot spots. In the case of Target 21, Orc1/Sir1, this resulted in a successful docking prediction(More)
Protein kinases represent a family of enzymes that are critical in cell signaling. One mechanism by which protein kinases are regulated is via autophosphorylation. In the studies described here, we have examined the mechanism of autophosphosphorylation at serine 338 in the regulation of protein kinase A (PKA). Expressed protein ligation allowed for the(More)
In CAPRI rounds 13-19, the most native-like structure predicted by RosettaDock resulted in two high, one medium, and one acceptable accuracy model out of 13 targets. The current rounds of CAPRI were especially challenging with many unbound and homology modeled starting structures. Novel docking methods, including EnsembleDock and SnugDock, allowed backbone(More)
Temperature-based replica-exchange molecular dynamics (REMD), in which multiple simultaneous simulations, or replicas, are run at a range of temperatures, has become increasingly popular for exploring the energy landscape of biomolecular systems. The practical application of REMD toward systems of biomedical interest is often limited by the rapidly(More)