Protein Structure Prediction Using Basin-Hopping

Associative memory Hamiltonian structure prediction potentials are not overly rugged, thereby suggesting their landscapes are like those of actual proteins. In the present contribution we show how basin-hopping global optimization can identify low-lying minima for the corresponding mildly frustrated energy landscapes. For small systems the basin-hopping algorithm succeeds in locating both lower minima and conformations closer to the experimental structure than does molecular dynamics with simulated annealing. For large systems the efficiency of basin-hopping decreases for our initial implementation, where the steps consist of random perturbations to the Cartesian coordinates. We implemented umbrella sampling using basin-hopping to further confirm when the global minima are reached. We have also improved the energy surface by employing bioinformatic techniques for reducing the roughness or variance of the energy surface. Finally, the basin-hopping calculations have guided improvements in the excluded volume of the Hamiltonian, producing better structures. These results suggest a novel and transferable optimization scheme for future energy function development

Communication: optimal parameters for basin-hopping global optimization based on Tsallis statistics.

A fundamental problem associated with global optimization is the large free energy barrier for the corresponding solid-solid phase transitions for systems with multi-funnel energy landscapes. To address this issue we consider the Tsallis weight instead of the Boltzmann weight to define the acceptance ratio for basin-hopping global optimization. Benchmarks for atomic clusters show that using the optimal Tsallis weight can improve the efficiency by roughly a factor of two. We present a theory that connects the optimal parameters for the Tsallis weighting, and demonstrate that the predictions are verified for each of the test cases.This work was supported by the ERC and the EPSRC.This is the accepted manuscript version of the article. Copyright 2014 American Institute of Physics. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the American Institute of Physics. The following article appeared in J. Chem. Phys. 141, 071101 (2014) and may be found at http://dx.doi.org/10.1063/1.4893344

Stacked clusters of polycyclic aromatic hydrocarbon molecules

Clusters of polycyclic aromatic hydrocarbon (PAH) molecules are modelled using explicit all-atom potentials using a rigid body approximation. The PAH's considered range from pyrene (C10H8) to circumcoronene (C54H18), and clusters containing between 2 and 32 molecules are investigated. In addition to the usual repulsion-dispersion interactions, electrostatic point-charge interactions are incorporated, as obtained from density functional theory calculations. The general electrostatic distribution in neutral or singly charged PAH's is reproduced well using a fluctuating charges analysis, which provides an adequate description of the multipolar distribution. Global optimization is performed using a variety of methods, including basin-hopping and parallel tempering Monte Carlo. We find evidence that stacking the PAH molecules generally yields the most stable motif. A structural transition between one-dimensional stacks and three-dimensional shapes built from mutiple stacks is observed at larger sizes, and the threshold for this transition increases with the size of the monomer. Larger aggregates seem to evolve toward the packing observed for benzene in bulk.Difficulties met in optimizing these clusters are analysed in terms of the strong anisotropy of the molecules. We also discuss segregation in heterogeneous clusters and vibrational properties in the context of astrophysical observations.Comment: 12 pages, 7 figure

A concept for a fuel efficient flight planning aid for general aviation

A core equation for estimation of fuel burn from path profile data was developed. This equation was used as a necessary ingredient in a dynamic program to define a fuel efficient flight path. The resultant algorithm is oriented toward use by general aviation. The pilot provides a description of the desired ground track, standard aircraft parameters, and weather at selected waypoints. The algorithm then derives the fuel efficient altitudes and velocities at the waypoints

Particle rearrangements during transitions between local minima of the potential energy landscape of a supercooled Lennard-Jones liquid

The potential energy landscape (PEL) of supercooled binary Lennard-Jones (BLJ) mixtures exhibits local minima, or inherent structures (IS), which are organized into meta-basins (MB). We study the particle rearrangements related to transitions between both successive IS and successive MB for a small 80:20 BLJ system near the mode-coupling temperature T_MCT. The analysis includes the displacements of individual particles, the localization of the rearrangements and the relevance of string-like motion. We find that the particle rearrangements during IS and MB transitions do not change significantly at T_MCT. Further, it is demonstrated that IS and MB dynamics are spatially heterogeneous and facilitated by string-like motion. To investigate the mechanism of string-like motion, we follow the particle rearrangements during suitable sequences of IS transitions. We find that most strings observed after a series of transitions do not move coherently during a single transition, but subunits of different sizes are active at different times. Several findings suggest that the occurrence of a successful string enables the system to exit a MB. Moreover, we show that the particle rearrangements during two consecutive MB transitions are basically uncorrelated. Specifically, different groups of particles are highly mobile during subsequent MB transitions. Finally, the relation between the features of the PEL and the relaxation processes in supercooled liquids is discussed.Comment: 13 pages, 10 figure

Prediction of long and short time rheological behavior in soft glassy materials

We present an effective time approach to predict long and short time rheological behavior of soft glassy materials from experiments carried out over practical time scales. Effective time approach takes advantage of relaxation time dependence on aging time that allows time-aging time superposition even when aging occurs over the experimental timescales. Interestingly experiments on variety of soft materials demonstrate that the effective time approach successfully predicts superposition for diverse aging regimes ranging from sub-aging to hyper-aging behaviors. This approach can also be used to predict behavior of any response function in molecular as well as spin glasses.Comment: 13 pages, 4 figure

The Energy Landscape, Folding Pathways and the Kinetics of a Knotted Protein

The folding pathway and rate coefficients of the folding of a knotted protein are calculated for a potential energy function with minimal energetic frustration. A kinetic transition network is constructed using the discrete path sampling approach, and the resulting potential energy surface is visualized by constructing disconnectivity graphs. Owing to topological constraints, the low-lying portion of the landscape consists of three distinct regions, corresponding to the native knotted state and to configurations where either the N- or C-terminus is not yet folded into the knot. The fastest folding pathways from denatured states exhibit early formation of the N-terminus portion of the knot and a rate-determining step where the C-terminus is incorporated. The low-lying minima with the N-terminus knotted and the C-terminus free therefore constitute an off-pathway intermediate for this model. The insertion of both the N- and C-termini into the knot occur late in the folding process, creating large energy barriers that are the rate limiting steps in the folding process. When compared to other protein folding proteins of a similar length, this system folds over six orders of magnitude more slowly.Comment: 19 page

Network of inherent structures in spin glasses: scaling and scale-free distributions

The local minima (inherent structures) of a system and their associated transition links give rise to a network. Here we consider the topological and distance properties of such a network in the context of spin glasses. We use steepest descent dynamics, determining for each disorder sample the transition links appearing within a given barrier height. We find that differences between linked inherent structures are typically associated with local clusters of spins; we interpret this within a framework based on droplets in which the characteristic ``length scale'' grows with the barrier height. We also consider the network connectivity and the degrees of its nodes. Interestingly, for spin glasses based on random graphs, the degree distribution of the network of inherent structures exhibits a non-trivial scale-free tail.Comment: minor changes and references adde

Home accidents amongst elderly people: A locality study in Scotland

Aim The aim of this locality study was to collect information on reported and unreported accidents amongst elderly people living in one locality in Scotland. Method Postal Survey- A postal questionnaire was sent to 3,757 men and women aged 65+ years living in one locality. The questionnaire asked respondents to indicate how many accidents they had experienced in the past twelve months, plus to indicate type and location. Information was gathered on living arrangements, ethnicity, gender, age and deprivation. Respondents were asked if they would be willing to take part in an interview study. Interview Study - One hundred elders who had had at least one accident in the previous twelve months were interviewed. Results Postal Survey - Over a third of the respondents in the postal survey reported having had an accident in the previous twelve months. Bumps and drops and falls were the most common type of accident. Most accidents happened in the kitchen. Women reported more falls than men and those living alone reported more accidents than those living with others. Age was associated with the prevalence of accidents, but the association was somewhat curvilinear, with accidents decreasing with age and then increasing again. Interview Study – Interviewees found it hard to differentiate one accident from another. Considerable reluctance to visit the GP after an accident was noted, with many not attending even for serious accidents. Almost forty percent were ‘very’ distressed after their accident, and a quarter reported a loss of confidence. However, most did not worry about accidents. Few thought that their age, health or medications were a cause of their accidents

Noro-Frenkel scaling in short-range square well: A Potential Energy Landscape study

We study the statistical properties of the potential energy landscape of a system of particles interacting via a very short-range square-well potential (of depth $-u_0$), as a function of the range of attraction $\Delta$ to provide thermodynamic insights of the Noro and Frenkel [ M.G. Noro and D. Frenkel, J.Chem.Phys. {\bf 113}, 2941 (2000)] scaling. We exactly evaluate the basin free energy and show that it can be separated into a {\it vibrational} ($\Delta$-dependent) and a {\it floppy} ($\Delta$-independent) component. We also show that the partition function is a function of $\Delta e^{\beta u_o}$, explaining the equivalence of the thermodynamics for systems characterized by the same second virial coefficient. An outcome of our approach is the possibility of counting the number of floppy modes (and their entropy).Comment: 4 pages, 4 figures accepted for publication on PR