Diwakar Shukla

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OpenMM is a software toolkit for performing molecular simulations on a range of high performance computing architectures. It is based on a layered architecture: the lower layers function as a reusable library that can be invoked by any application, while the upper layers form a complete environment for running molecular simulations. The library API hides(More)
CONSPECTUS: Protein function is inextricably linked to protein dynamics. As we move from a static structural picture to a dynamic ensemble view of protein structure and function, novel computational paradigms are required for observing and understanding conformational dynamics of proteins and its functional implications. In principle, molecular dynamics(More)
Unregulated activation of Src kinases leads to aberrant signalling, uncontrolled growth and differentiation of cancerous cells. Reaching a complete mechanistic understanding of large-scale conformational transformations underlying the activation of kinases could greatly help in the development of therapeutic drugs for the treatment of these pathologies. In(More)
Simulations can provide tremendous insight into the atomistic details of biological mechanisms, but micro- to millisecond timescales are historically only accessible on dedicated supercomputers. We demonstrate that cloud computing is a viable alternative that brings long-timescale processes within reach of a broader community. We used Google's Exacycle(More)
Quantitatively accurate all-atom molecular dynamics (MD) simulations of protein folding have long been considered a holy grail of computational biology. Due to the large system sizes and long timescales involved, such a pursuit was for many years computationally intractable. Further, sufficiently accurate forcefields needed to be developed in order to(More)
Much work has been performed on understanding the effects of additives on protein thermodynamics and degradation kinetics, in particular addressing the Hofmeister series and other broad empirical phenomena. Little attention, however, has been paid to the effect of additive-additive interactions on proteins. Our group and others have recently shown that such(More)
Aqueous arginine solutions are used extensively for inhibiting protein aggregation. There are several theories proposed to explain the effect of arginine on protein stability, but the exact mechanism is still not clear. To understand the mechanism of protein cosolvent interaction, the intraprotein, protein-solvent, and intrasolvent interactions have to be(More)
Protein based therapeutics hold great promise in the treatment of human diseases and disorders and subsequently, they have become the fastest growing sector of new drugs being developed. Proteins are, however, inherently unstable and the degraded form can be quite harmful if administered to a patient. Of the various degradation pathways, aggregation is one(More)
Estimation of the thermodynamic properties of proteins in mixed solvents is crucial for understanding the effect of cosolvents on rates and equilibrium constants of reactions involving proteins. In this paper, a predictive, molecular level approach for the study of preferential interactions of proteins with either water or cosolvents based on all-atom,(More)
L-Arginine hydrochloride is a very important aggregation suppressor for which there has been much attention given regarding elucidating its mechanism of action. Little consideration, however, has been given toward other salt forms besides chloride, even though the counterion likely imparts a large influence per the Hofmeister Series. Here, we report an in(More)