Beyond rotamers: a generative, probabilistic model of side chains in proteins.

RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.BACKGROUND: Accurately covering the conformational space of amino acid side chains is essential for important applications such as protein design, docking and high resolution structure prediction. Today, the most common way to capture this conformational space is through rotamer libraries - discrete collections of side chain conformations derived from experimentally determined protein structures. The discretization can be exploited to efficiently search the conformational space. However, discretizing this naturally continuous space comes at the cost of losing detailed information that is crucial for certain applications. For example, rigorously combining rotamers with physical force fields is associated with numerous problems. RESULTS: In this work we present BASILISK: a generative, probabilistic model of the conformational space of side chains that makes it possible to sample in continuous space. In addition, sampling can be conditional upon the protein's detailed backbone conformation, again in continuous space - without involving discretization. CONCLUSIONS: A careful analysis of the model and a comparison with various rotamer libraries indicates that the model forms an excellent, fully continuous model of side chain conformational space. We also illustrate how the model can be used for rigorous, unbiased sampling with a physical force field, and how it improves side chain prediction when used as a pseudo-energy term. In conclusion, BASILISK is an important step forward on the way to a rigorous probabilistic description of protein structure in continuous space and in atomic detail

The Case for Distributed Engine Control in Turbo-Shaft Engine Systems

The turbo-shaft engine is an important propulsion system used to power vehicles on land, sea, and in the air. As the power plant for many high performance helicopters, the characteristics of the engine and control are critical to proper vehicle operation as well as being the main determinant to overall vehicle performance. When applied to vertical flight, important distinctions exist in the turbo-shaft engine control system due to the high degree of dynamic coupling between the engine and airframe and the affect on vehicle handling characteristics. In this study, the impact of engine control system architecture is explored relative to engine performance, weight, reliability, safety, and overall cost. Comparison of the impact of architecture on these metrics is investigated as the control system is modified from a legacy centralized structure to a more distributed configuration. A composite strawman system which is typical of turbo-shaft engines in the 1000 to 2000 hp class is described and used for comparison. The overall benefits of these changes to control system architecture are assessed. The availability of supporting technologies to achieve this evolution is also discussed

Reconstructing protein structure from solvent exposure using tabu search

BACKGROUND: A new, promising solvent exposure measure, called half-sphere-exposure (HSE), has recently been proposed. Here, we study the reconstruction of a protein's C(α )trace solely from structure-derived HSE information. This problem is of relevance for de novo structure prediction using predicted HSE measure. For comparison, we also consider the well-established contact number (CN) measure. We define energy functions based on the HSE- or CN-vectors and minimize them using two conformational search heuristics: Monte Carlo simulation (MCS) and tabu search (TS). While MCS has been the dominant conformational search heuristic in literature, TS has been applied only a few times. To discretize the conformational space, we use lattice models with various complexity. RESULTS: The proposed TS heuristic with a novel tabu definition generally performs better than MCS for this problem. Our experiments show that, at least for small proteins (up to 35 amino acids), it is possible to reconstruct the protein backbone solely from the HSE or CN information. In general, the HSE measure leads to better models than the CN measure, as judged by the RMSD and the angle correlation with the native structure. The angle correlation, a measure of structural similarity, evaluates whether equivalent residues in two structures have the same general orientation. Our results indicate that the HSE measure is potentially very useful to represent solvent exposure in protein structure prediction, design and simulation

Application of aerial photographs for the assessment of anthropogenic denudation impact on soil cover of the Brodnica Landscape Park plateau areas

The aim of the study was to assess suitability of colour aerial photographs for mapping of soil cover transformed due to effect of anthropogenic denudation. The investigation was carried out in south-western part of the Brodnica Landscape Park, within the boundaries of rolling and hilly moraine plateau, used for agricultural purposes. The soil cover of that area is exposed to intensive influence of slope processes triggered by human agricultural activity. The anthropogenic denudation leads to truncation of soil profiles of top convex sections of slopes and hills’ summits. Soil material moved down the slopes is accumulated in the form of diluvium in hollows and lower sections of slopes. Two study sites were selected – Sumówko and Zbiczno. Within the boundaries of both study sites, detailed soil mapping took place consisting in preparation of irregular boreholes projection. Next, four sites were selected for soil pits, representing broad spectrum of transformations related to anthropogenic denudation. Based on obtained results and colour diversity of surface horizons, the spatial range of individual soil types was specified. It also enabled determination of anthropogenic denudation impact on formation of the soil cover. Totally eroded soils, classified as pelosols, located on hills’ summits, are characterized by very bright colours of surface horizons, resulting from content of calcium carbonate in glacial tills. The range of soil lessivés, prevailing within the slopes boundaries, where the erosion resulted in exposure of argic horizons rich in iron compounds and clay fraction, coincided with occurrence of brown colours. Bright grey surface horizons are characteristic of deluvial soils. This colour arises from sandy texture of deluvial material (low content of iron) in combination with humus nature. The soils located in relatively vast field depressions were covered with small thickness of diluvium, which was reflected in dark grey colours of surface horizons. These horizons are relatively rich in soil humus. Significant amounts of humus are related with mix of deluvial material with material formed in humus horizons, originally occurring on surfaces of soils rich in organic matter – black earths and organic soils.

Potentials of Mean Force for Protein Structure Prediction Vindicated, Formalized and Generalized

Understanding protein structure is of crucial importance in science, medicine and biotechnology. For about two decades, knowledge based potentials based on pairwise distances -- so-called "potentials of mean force" (PMFs) -- have been center stage in the prediction and design of protein structure and the simulation of protein folding. However, the validity, scope and limitations of these potentials are still vigorously debated and disputed, and the optimal choice of the reference state -- a necessary component of these potentials -- is an unsolved problem. PMFs are loosely justified by analogy to the reversible work theorem in statistical physics, or by a statistical argument based on a likelihood function. Both justifications are insightful but leave many questions unanswered. Here, we show for the first time that PMFs can be seen as approximations to quantities that do have a rigorous probabilistic justification: they naturally arise when probability distributions over different features of proteins need to be combined. We call these quantities reference ratio distributions deriving from the application of the reference ratio method. This new view is not only of theoretical relevance, but leads to many insights that are of direct practical use: the reference state is uniquely defined and does not require external physical insights; the approach can be generalized beyond pairwise distances to arbitrary features of protein structure; and it becomes clear for which purposes the use of these quantities is justified. We illustrate these insights with two applications, involving the radius of gyration and hydrogen bonding. In the latter case, we also show how the reference ratio method can be iteratively applied to sculpt an energy funnel. Our results considerably increase the understanding and scope of energy functions derived from known biomolecular structures

SAM-T08, HMM-based protein structure prediction

The SAM-T08 web server is a protein structure prediction server that provides several useful intermediate results in addition to the final predicted 3D structure: three multiple sequence alignments of putative homologs using different iterated search procedures, prediction of local structure features including various backbone and burial properties, calibrated E-values for the significance of template searches of PDB and residue–residue contact predictions. The server has been validated as part of the CASP8 assessment of structure prediction as having good performance across all classes of predictions. The SAM-T08 server is available at http://compbio.soe.ucsc.edu/SAM_T08/T08-query.htm