arXiv subjects

Vijay S. Pande

Publications and source records attributed to Vijay S. Pande.

45 records · Page 3Linked to original sources

arXiv2011

Splitting probabilities as a test of reaction coordinate choice in single-molecule experiments

To explain the observed dynamics in equilibrium single-molecule measurements of biomolecules, the experimental observable is often chosen as a putative reaction coordinate along which kinetic behavior is presumed to be governed by diffusive dynamics. Here, we invoke the splitting probability as a test of the suitability of such a proposed reaction coordinate. Comparison of the observed splitting probability with that computed from the kinetic model provides a simple test to reject poor reaction coordinates. We demonstrate this test for a force spectroscopy measurement of a DNA hairpin.

cond-mat.stat-mech↗

arXiv2010

A simple theory of protein folding kinetics

We present a simple model of protein folding dynamics that captures key qualitative elements recently seen in all-atom simulations. The goals of this theory are to serve as a simple formalism for gaining deeper insight into the physical properties seen in detailed simulations as well as to serve as a model to easily compare why these simulations suggest a different kinetic mechanism than previous simple models. Specifically, we find that non-native contacts play a key role in determining the mechanism, which can shift dramatically as the energetic strength of non-native interactions is changed. For protein-like non-native interactions, our model finds that the native state is a kinetic hub, connecting the strength of relevant interactions directly to the nature of folding kinetics.

physics.bio-ph↗

arXiv2009

Hard Data on Soft Errors: A Large-Scale Assessment of Real-World Error Rates in GPGPU

Graphics processing units (GPUs) are gaining widespread use in computational chemistry and other scientific simulation contexts because of their huge performance advantages relative to conventional CPUs. However, the reliability of GPUs in error-intolerant applications is largely unproven. In particular, a lack of error checking and correcting (ECC) capability in the memory subsystems of graphics cards has been cited as a hindrance to the acceptance of GPUs as high-performance coprocessors, but the impact of this design has not been previously quantified. In this article we present MemtestG80, our software for assessing memory error rates on NVIDIA G80 and GT200-architecture-based graphics cards. Furthermore, we present the results of a large-scale assessment of GPU error rate, conducted by running MemtestG80 on over 20,000 hosts on the Folding@home distributed computing network. Our control experiments on consumer-grade and dedicated-GPGPU hardware in a controlled environment found no errors. However, our survey over cards on Folding@home finds that, in their installed environments, two-thirds of tested GPUs exhibit a detectable, pattern-sensitive rate of memory soft errors. We demonstrate that these errors persist after controlling for overclocking and environmental proxies for temperature, but depend strongly on board architecture.

cs.AR↗

arXiv2009

Folding@Home and Genome@Home: Using distributed computing to tackle previously intractable problems in computational biology

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, we review novel methods to fundamentally speed such previously intractable problems using a new computational paradigm: distributed computing. By efficiently harnessing tens of thousands of computers throughout the world, we have been able to break previous computational barriers. However, distributed computing brings new challenges, such as how to efficiently divide a complex calculation of many PCs that are connected by relatively slow networking. Moreover, even if the challenge of accurately reproducing reality can be conquered, a new challenge emerges: how can we take the results of these simulations (typically tens to hundreds of gigabytes of raw data) and gain some insight into the questions at hand. This challenge of the analysis of the sea of data resulting from large-scale simulation will likely remain for decades to come.

physics.bio-ph↗

arXiv2008

Potential for modulation of the hydrophobic effect inside chaperonins

Despite the spontaneity of some in vitro protein folding reactions, native folding in vivo often requires the participation of barrel-shaped multimeric complexes known as chaperonins. Although it has long been known that chaperonin substrates fold upon sequestration inside the chaperonin barrel, the precise mechanism by which confinement within this space facilitates folding remains unknown. In this study, we examine the possibility that the chaperonin mediates a favorable reorganization of the solvent for the folding reaction. We begin by discussing the effect of electrostatic charge on solvent-mediated hydrophobic forces in an aqueous environment. Based on these initial physical arguments, we construct a simple, phenomenological theory for the thermodynamics of density and hydrogen bond order fluctuations in liquid water. Within the framework of this model, we investigate the effect of confinement within a chaperonin-like cavity on the configurational free energy of water by calculating solvent free energies for cavities corresponding to the different conformational states in the ATP- driven catalytic cycle of the prokaryotic chaperonin GroEL. Our findings suggest that one function of chaperonins may be to trap unfolded proteins and subsequently expose them to a micro-environment in which the hydrophobic effect, a crucial thermodynamic driving force for folding, is enhanced.

q-bio.BM↗

arXiv1996

Freezing Transition of Compact Polyampholytes

Polyampholytes (PAs) are heteropolymers with long range Coulomb interactions. Unlike polymers with short range forces, PA energy levels have non-vanishing correlations and are thus very different from the Random Energy Model (REM). Nevertheless, if charges in the PA globule are screened as in a regular plasma, PAs freeze in REM fashion. Our results shed light on the potential role of Coulomb interactions in folding and evolution of {\it proteins}, which are weakly charged PAs, in particular making connection with the finding that sequences of charged amino acids in proteins are not random.

cond-mat↗

arXiv1996

Is Heteropolymer Freezing Well Described by the Random Energy Model?

It is widely held that the Random Energy Model (REM) describes the freezing transition of a variety of types of heteropolymers. We demonstrate that the hallmark property of REM, statistical independence of the energies of states over disorder, is violated in different ways for models commonly employed in heteropolymer freezing studies. The implications for proteins are also discussed.

cond-mat↗

arXiv1995

How Accurate Must Potentials Be for Successful Modeling of Protein Folding?

Protein sequences are believed to have been selected to provide the stability of, and reliable renaturation to, an encoded unique spatial fold. In recently proposed theoretical schemes, this selection is modeled as ``minimal frustration,'' or ``optimal energy'' of the desirable target conformation over all possible sequences, such that the ``design'' of the sequence is governed by the interactions between monomers. With replica mean field theory, we examine the possibility to reconstruct the renaturation, or freezing transition, of the ``designed'' heteropolymer given the inevitable errors in the determination of interaction energies, that is, the difference between sets (matrices) of interactions governing chain design and conformations, respectively. We find that the possibility of folding to the designed conformation is controlled by the correlations of the elements of the design and renaturation interaction matrices; unlike random heteropolymers, the ground state of designed heteropolymers is sufficiently stable, such that even a substantial error in the interaction energy should still yield correct renaturation.

cond-mat↗

arXiv1994

Freezing Transition of Random Heteropolymers Consisting of an Arbitrary Set of Monomers

Mean field replica theory is employed to analyze the freezing transition of random heteropolymers comprised of an arbitrary number ($q$) of types of monomers. Our formalism assumes that interactions are short range and heterogeneity comes only from pairwise interactions, which are defined by an arbitrary $q \times q$ matrix. We show that, in general, there exists a freezing transition from a random globule, in which the thermodynamic equilibrium is comprised of an essentially infinite number polymer conformations, to a frozen globule, in which equilibrium ensemble is dominated by one or very few conformations. We also examine some special cases of interaction matrices to analyze the relationship between the freezing transition and the nature of interactions involved.

cond-mat↗