Vijay S. Pande

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For decades, researchers have been applying computer simulation to address problems in biology. However, many of these “grand challenges” in computational biology, such as simulating how proteins fold, remained unsolved due to their great complexity. Indeed, even to simulate the fastest folding protein would require decades on the fastest modern CPUs. Here,(More)
The ensemble folding of two 21-residue alpha-helical peptides has been studied using all-atom simulations under several variants of the AMBER potential in explicit solvent using a global distributed computing network. Our extensive sampling, orders of magnitude greater than the experimental folding time, results in complete convergence to ensemble(More)
To meet the challenge of modeling the conformational dynamics of biological macromolecules over long time scales, much recent effort has been devoted to constructing stochastic kinetic models, often in the form of discrete-state Markov models, from short molecular dynamics simulations. To construct useful models that faithfully represent dynamics at the(More)
Spectroscopic studies have identified a number of proteins that appear to retain significant residual structure under even strongly denaturing conditions. Intrinsic viscosity, hydrodynamic radii, and small-angle x-ray scattering studies, in contrast, indicate that the dimensions of most chemically denatured proteins scale with polypeptide length by means of(More)
Accurate simulation of biophysical processes requires vast computing resources. Folding@home is a distributed computing system first released in 2000 to provide such resources needed to simulate protein folding and other biomolecular phenomena. Now operating in the range of 5 PetaFLOPS sustained, it provides more computing power than can typically be(More)
We have performed molecular dynamics simulations on a set of nine unfolded conformations of the fastest-folding protein yet discovered, a variant of the villin headpiece subdomain (HP-35 NleNle). The simulations were generated using a new distributed computing method, yielding hundreds of trajectories each on a time scale comparable to the experimental(More)
Atomistic simulations of protein folding have the potential to be a great complement to experimental studies, but have been severely limited by the time scales accessible with current computer hardware and algorithms. By employing a worldwide distributed computing network of tens of thousands of PCs and algorithms designed to efficiently utilize this new(More)
By employing thousands of PCs and new worldwide-distributed computing techniques, we have simulated in atomistic detail the folding of a fast-folding 36-residue alpha-helical protein from the villin headpiece. The total simulated time exceeds 300 micros, orders of magnitude more than previous simulations of a molecule of this size. Starting from an extended(More)
Lipid membrane fusion is critical to cellular transport and signaling processes such as constitutive secretion, neurotransmitter release, and infection by enveloped viruses. Here, we introduce a powerful computational methodology for simulating membrane fusion from a starting configuration designed to approximate activated prefusion assemblies from neuronal(More)
Part of understanding a molecule's conformational dynamics is mapping out the dominant metastable, or long lived, states that it occupies. Once identified, the rates for transitioning between these states may then be determined in order to create a complete model of the system's conformational dynamics. Here we describe the use of the MSMBuilder package(More)