Biomedical subjects

M Scott Shell

Publications and source records attributed to M Scott Shell.

6 recordsLinked to original sources

PubMed2006

Computational characterization of the sequence landscape in simple protein alphabets.

We characterize the "sequence landscapes" in several simple, heteropolymer models of proteins by examining their mutation properties. Using an efficient flat-histogram Monte Carlo search method, our approach involves determining the distribution in energy of all sequences of a given length when threaded through a common backbone. These calculations are performed for a number of Protein Data Bank structures using two variants of the 20-letter contact potential developed by Miyazawa and Jernigan [Miyazawa S, Jernigan WL. Macromolecules 1985;18:534], and the 2-monomer HP model of Lau and Dill [Lau KF, Dill KA. Macromolecules 1989;22:3986]. Our results indicate significant differences among the energy functions in terms of the "smoothness" of their landscapes. In particular, one of the Miyazawa-Jernigan contact potentials reveals unusual cooperative behavior among its species' interactions, resulting in what is essentially a set of phase transitions in sequence space. Our calculations suggest that model-specific features can have a profound effect on protein design algorithms, and our methods offer a number of ways by which sequence landscapes can be quantified.

Amino Acid Sequence↗

PubMed2005

Novel computational probes of diffusive motion.

Self-diffusion constants, D, and the atomic-level processes that produce them have been investigated numerically for the binary-mixture Lennard-Jones (BMLJ) model and for liquid silica as described by the Van Beest-Kramer-Van Santen interaction model. The primary conceptual tool for this study is the joint probability distribution for single particles as a function of initial velocity and positional displacement at a given later instant. Self-diffusion constants can be expressed exactly in terms of this probability function. The numerical simulations for the BMLJ case reveal an unusual temperature effect; in contrast to the high-temperature behavior, particles with high initial velocities experience disproportionate retardation in forward displacement. In the silica modeling simulations, diffusive processes have been compared at constant-temperature "isodiffusive" pairs of states, demonstrating a significant role played by the amount of local tetrahedral order that is present in the medium.

Journal Article↗

PubMed2004

Thermodynamics and the glass transition in model energy landscapes.

We determine the liquid-state thermodynamics for a model energy landscape corresponding to soft spheres with a mean-field attraction. We consider two approximations, in which the distribution of potential energy minima is either Gaussian or binomial, and for each we calculate the liquid spinodal, binodal, and "effective" glass transition locus. The resulting models provide a unified description of the liquid state across the complete range from low-temperature glassiness to high-temperature instability with respect to the vapor phase.

Journal Article↗

PubMed2004

Saddles in the energy landscape: extensivity and thermodynamic formalism.

We formally extend the energy landscape approach for the thermodynamics of liquids to account for saddle points. By considering the extensive nature of macroscopic potential energies, we derive the scaling behavior of saddles with system size, as well as several approximations for the properties of low-order saddles (i.e., those with only a few unstable directions). We then cast the canonical partition function in a saddle-explicit form and develop, for the first time, a rigorous energy landscape approach capable of reproducing trends observed in simulations, in particular, the temperature dependence of the energy and fractional order of sampled saddles.

Journal Article↗

PubMed2002

Generalization of the Wang-Landau method for off-lattice simulations.

We present a rigorous derivation for off-lattice implementations of the so-called "random-walk" algorithm recently introduced by Wang and Landau [Phys. Rev. Lett. 86, 2050 (2001)]. Originally developed for discrete systems, the algorithm samples configurations according to their inverse density of states using Monte Carlo moves; the estimate for the density of states is refined at each simulation step and is ultimately used to calculate thermodynamic properties. We present an implementation for atomic systems based on a rigorous separation of kinetic and configurational contributions to the density of states. By constructing a "uniform" ensemble for configurational degrees of freedom-in which all potential energies, volumes, and numbers of particles are equally probable-we establish a framework for the correct implementation of simulation acceptance criteria and calculation of thermodynamic averages in the continuum case. To demonstrate the generality of our approach, we perform sample calculations for the Lennard-Jones fluid using two implementation variants and in both cases find good agreement with established literature values for the vapor-liquid coexistence locus.

Journal Article↗

PubMed2002

Molecular structural order and anomalies in liquid silica.

The present investigation examines the relationship between structural order, diffusivity anomalies, and density anomalies in liquid silica by means of molecular dynamics simulations. We use previously defined orientational and translational order parameters to quantify local structural order in atomic configurations. Extensive simulations are performed at different state points to measure structural order, diffusivity, and thermodynamic properties. It is found that silica shares many trends recently reported for water [J. R. Errington and P. G. Debenedetti, Nature 409, 318 (2001)]. At intermediate densities, the distribution of local orientational order is bimodal. At fixed temperature, order parameter extrema occur upon compression: a maximum in orientational order followed by a minimum in translational order. Unlike water, however, silica's translational order parameter minimum is broad, and there is no range of thermodynamic conditions where both parameters are strictly coupled. Furthermore, the temperature-density regime where both structural order parameters decrease upon isothermal compression (the structurally anomalous regime) does not encompass the region of diffusivity anomalies, as was the case for water.

Journal Article↗