Relevant distance between two different instances of the same potential energy in protein folding

In the context of complex systems and, particularly, of protein folding, a physically meaningful distance is defined which allows to make useful statistical statements about the way in which energy differences are modified when two different instances of the same potential-energy function are used. When the two instances arise from the fact that different algorithms or different approximations are used, the distance herein defined may be used to evaluate the relative accuracy of the two methods. When the difference is due to a change in the free parameters of which the potential depends on, the distance can be used to quantify, in each region of parameter space, the robustness of the modeling to such a change and this, in turn, may be used to assess the significance of a parameters' fit. Both cases are illustrated with a practical example: the study of the Poisson-based solvation energy in the Trp-Cage protein (PDB code 1L2Y).Comment: 20 pages, 6 figures, LaTeX file, elsart style. v1: Aknowledgments modified. v2: y-values of fig. 5 and 6 corrected. v3: Journal-ref added, aknowledgements modified and fig. 1 and 2 correcte

Gateway to offending behaviour: permission-giving thoughts of online users of child sexual exploitation material.

The endorsement of permission-giving thoughts, or so-called cognitive distortions, has been discussed as a contributing factor in sexually abusive behaviour. The current study set out to explore the thinking patterns of offenders who have used/downloaded child sexual exploitation material (CSEM), based on a survey of professionals. A thematic analysis elicited four overarching themes, namely the Perceived Nature of Children (perception of children portrayed in CSEM, as well as children in general), Non-sexual Engagement with CSEM (motivating factors that are not inherently sexual in nature), Denial of Harm (perception of the level of harm caused by CSEM), and Expression of a General Sexual Preference (general interest in deviant sexual behaviour). These themes aid to explore the differences and similarities between contact and non-contact offenders and to improve the understanding of the role of permission-giving thoughts in this offending. Results are discussed in terms of their theoretical significance and future implications

Four small puzzles that Rosetta doesn't solve

A complete macromolecule modeling package must be able to solve the simplest structure prediction problems. Despite recent successes in high resolution structure modeling and design, the Rosetta software suite fares poorly on deceptively small protein and RNA puzzles, some as small as four residues. To illustrate these problems, this manuscript presents extensive Rosetta results for four well-defined test cases: the 20-residue mini-protein Trp cage, an even smaller disulfide-stabilized conotoxin, the reactive loop of a serine protease inhibitor, and a UUCG RNA tetraloop. In contrast to previous Rosetta studies, several lines of evidence indicate that conformational sampling is not the major bottleneck in modeling these small systems. Instead, approximations and omissions in the Rosetta all-atom energy function currently preclude discriminating experimentally observed conformations from de novo models at atomic resolution. These molecular "puzzles" should serve as useful model systems for developers wishing to make foundational improvements to this powerful modeling suite.Comment: Published in PLoS One as a manuscript for the RosettaCon 2010 Special Collectio

Identification of five fundamental implicit theories underlying cognitive distortions in child abusers : a preliminary study

Qualitative analysis of interviews with 22 child abusers found strong evidence for Ward and Keenan\u27s (1999) proposal that there are five implicit theories in child abusers that account for the majority of their cognitive distortions/thinking errors. These implicit theories are: Child as a sexual being where children are perceived as being able to and wanting to engage in sexual activity with adults and also are not be harmed by such sexual contact; Nature of harm where the offender perceives that sexual activity does not cause harm (and may in fact be beneficial) to the child; Entitlement where the child abuser perceives that he is superior and more important than others: and hence is able to have sex with whoever, and whenever, he wants; Dangerous world where the offender perceives that that others are abusive and rejecting and he must fight to regain control; and Uncontrollable where the offender perceives the world as uncontrollable and hence he believes that circumstances are outside of his control. There was no evidence for any other type of implicit theory. Results of the study also indicated that there was a significant difference in terms of the endorsement of the Dangerous world implicit theory between participants reporting a history of child sexual abuse and those who did not. Offenders against male victims were significantly more likely to endorse the Child as a sexual being and Dangerous world implicit theories compared to men who had offended against female children

An effective all-atom potential for proteins

We describe and test an implicit solvent all-atom potential for simulations of protein folding and aggregation. The potential is developed through studies of structural and thermodynamic properties of 17 peptides with diverse secondary structure. Results obtained using the final form of the potential are presented for all these peptides. The same model, with unchanged parameters, is furthermore applied to a heterodimeric coiled-coil system, a mixed alpha/beta protein and a three-helix-bundle protein, with very good results. The computational efficiency of the potential makes it possible to investigate the free-energy landscape of these 49--67-residue systems with high statistical accuracy, using only modest computational resources by today's standards

Wall conditions in ORMAK

From surface effects in controlled thermonuclear fusion devices and reactors meeting; Argonne, Illnois, USA (10 Jan 1974). ORMAK is a diffuse toroidal pinch with typical plasma currents of 100 kA, electron temperatures of 800 eV, and ion temperatures of 300 eV. The walls of the plasma region are made of stainless steel coated with an intermediate layer of platinum 0.05 mu thick and an outer 1 to 2 mu layer of gold. Tests with an Ion Microprobe Mass Analyzer have shown that the platinum acts to decrease diffusion of impurities from the stalnless steel to the surface. Gold was chosen to inhibit the surface chemical adsorption of gases. Studies with a movable limiter indicate that electron energy is lost at the plasma edge mainly via line radiation and cooling on ions, while ions are lost from the plasma by charge exchange. Thus the walls are bombarded by energetic neutrals, line radiation and, in addition, bremsstrahlung x-rays. The flux of energetic neutrals is measured by a charge exchange analyzer. Wall bombardment by such neutrals should cause sputtering, and gold has been observed spectroscopically near the limiter, increasing with time during a shot, However, analysis of impurities coated on a window by the discharge indicated very little gold sputtering and re-deposition. To measure the sputterirg rate, a wall sample was coated with 105 A of radioactive gold and bombarded with neutrals from ORMAK during a day's run. No measurable sputtering was found within the counting statistics of the measurement, but surface carbon contamination of the sample prevented any final conclusions. (auth

An enhanced partial order curve comparison algorithm and its application to analyzing protein folding trajectories

<p>Abstract</p> <p>Background</p> <p>Understanding how proteins fold is essential to our quest in discovering how life works at the molecular level. Current computation power enables researchers to produce a huge amount of folding simulation data. Hence there is a pressing need to be able to interpret and identify novel folding features from them.</p> <p>Results</p> <p>In this paper, we model each folding trajectory as a multi-dimensional curve. We then develop an effective multiple curve comparison (MCC) algorithm, called the <it>enhanced partial order (EPO) </it>algorithm, to extract features from a set of diverse folding trajectories, including both successful and unsuccessful simulation runs. The EPO algorithm addresses several new challenges presented by comparing high dimensional curves coming from folding trajectories. A detailed case study on miniprotein Trp-cage <abbrgrp><abbr bid="B1">1</abbr></abbrgrp> demonstrates that our algorithm can detect similarities at rather low level, and extract biologically meaningful folding events.</p> <p>Conclusion</p> <p>The EPO algorithm is general and applicable to a wide range of applications. We demonstrate its generality and effectiveness by applying it to aligning multiple protein structures with low similarities. For user's convenience, we provide a web server for the algorithm at <url>http://db.cse.ohio-state.edu/EPO</url>.</p

Detection of Functional Modes in Protein Dynamics

Proteins frequently accomplish their biological function by collective atomic motions. Yet the identification of collective motions related to a specific protein function from, e.g., a molecular dynamics trajectory is often non-trivial. Here, we propose a novel technique termed “functional mode analysis” that aims to detect the collective motion that is directly related to a particular protein function. Based on an ensemble of structures, together with an arbitrary “functional quantity” that quantifies the functional state of the protein, the technique detects the collective motion that is maximally correlated to the functional quantity. The functional quantity could, e.g., correspond to a geometric, electrostatic, or chemical observable, or any other variable that is relevant to the function of the protein. In addition, the motion that displays the largest likelihood to induce a substantial change in the functional quantity is estimated from the given protein ensemble. Two different correlation measures are applied: first, the Pearson correlation coefficient that measures linear correlation only; and second, the mutual information that can assess any kind of interdependence. Detecting the maximally correlated motion allows one to derive a model for the functional state in terms of a single collective coordinate. The new approach is illustrated using a number of biomolecules, including a polyalanine-helix, T4 lysozyme, Trp-cage, and leucine-binding protein

Multiscale Coarse-Graining of the Protein Energy Landscape

A variety of coarse-grained (CG) models exists for simulation of proteins. An outstanding problem is the construction of a CG model with physically accurate conformational energetics rivaling all-atom force fields. In the present work, atomistic simulations of peptide folding and aggregation equilibria are force-matched using multiscale coarse-graining to develop and test a CG interaction potential of general utility for the simulation of proteins of arbitrary sequence. The reduced representation relies on multiple interaction sites to maintain the anisotropic packing and polarity of individual sidechains. CG energy landscapes computed from replica exchange simulations of the folding of Trpzip, Trp-cage and adenylate kinase resemble those of other reduced representations; non-native structures are observed with energies similar to those of the native state. The artifactual stabilization of misfolded states implies that non-native interactions play a deciding role in deviations from ideal funnel-like cooperative folding. The role of surface tension, backbone hydrogen bonding and the smooth pairwise CG landscape is discussed. Ab initio folding aside, the improved treatment of sidechain rotamers results in stability of the native state in constant temperature simulations of Trpzip, Trp-cage, and the open to closed conformational transition of adenylate kinase, illustrating the potential value of the CG force field for simulating protein complexes and transitions between well-defined structural states