CavVis-A Field-of-View Geometric Algorithm for Protein Cavity Detection.

Several geometric-based methods have been developed for the last two to three decades to detect and identify cavities (i.e., putative binding sites) on proteins, as needed to study protein-ligand interactions and protein docking. This paper introduces a new protein cavity method, called CavVis, which combines voxelization (i.e., a grid of voxels) and an analytic formulation of Gaussian surfaces that approximates the solvent-excluded surface. This method builds upon visibility of points on protein surface to find its cavities. Specifically, the visibility criterion combines three concepts we borrow from computer graphics, the field-of-view of each surface point, voxel ray casting, and back-face culling.

GPU-based detection of protein cavities using Gaussian surfaces.

BACKGROUND: Protein cavities play a key role in biomolecular recognition and function, particularly in protein-ligand interactions, as usual in drug discovery and design. Grid-based cavity detection methods aim at finding cavities as aggregates of grid nodes outside the molecule, under the condition that such cavities are bracketed by nodes on the molecule surface along a set of directions (not necessarily aligned with coordinate axes). Therefore, these methods are sensitive to scanning directions, a problem that we call cavity ground-and-walls ambiguity, i.e., they depend on the position and orientation of the protein in the discretized domain. Also, it is hard to distinguish grid nodes belonging to protein cavities amongst all those outside the protein, a problem that we call cavity ceiling ambiguity. RESULTS: We solve those two ambiguity problems using two implicit isosurfaces of the protein, the protein surface itself (called inner isosurface) that excludes all its interior nodes from any cavity, and the outer isosurface that excludes most of its exterior nodes from any cavity. Summing up, the cavities are formed from nodes located between these two isosurfaces. It is worth noting that these two surfaces do not need to be evaluated (i.e., sampled), triangulated, and rendered on the screen to find the cavities in between; their defining analytic functions are enough to determine which grid nodes are in the empty space between them. CONCLUSION: This article introduces a novel geometric algorithm to detect cavities on the protein surface that takes advantage of the real analytic functions describing two Gaussian surfaces of a given protein.

Efficient deformation algorithm for plasmid DNA simulations.

BACKGROUND: Plasmid DNA molecules are closed circular molecules that are widely used in life sciences, particularly in gene therapy research. Monte Carlo methods have been used for several years to simulate the conformational behavior of DNA molecules. In each iteration these simulation methods randomly generate a new trial conformation, which is either accepted or rejected according to a criterion based on energy calculations and stochastic rules. These simulation trials are generated using a method based on crankshaft motion that, apart from some slight improvements, has remained the same for many years. RESULTS: In this paper, we present a new algorithm for the deformation of plasmid DNA molecules for Monte Carlo simulations. The move underlying our algorithm preserves the size and connectivity of straight-line segments of the plasmid DNA skeleton. We also present the results of three experiments comparing our deformation move with the standard and biased crankshaft moves in terms of acceptance ratio of the trials, energy and temperature evolution, and average displacement of the molecule. Our algorithm can also be used as a generic geometric algorithm for the deformation of regular polygons or polylines that preserves the connections and lengths of their segments. CONCLUSION: Compared with both crankshaft moves, our move generates simulation trials with higher acceptance ratios and smoother deformations, making it suitable for real-time visualization of plasmid DNA coiling. For that purpose, we have adopted a DNA assembly algorithm that uses nucleotides as building blocks.

Outbreak of KPC-producing Klebsiella pneumoniae at a Portuguese university hospital: Epidemiological characterization and containment measures.

Background: KPC-producing K pneumoniae (KPC-Kp) is a public health problem with important clinical and epidemiological implications. We describe an outbreak of KPC-Kp at vascular surgery and neurosurgery wards in a central hospital in Porto, Portugal. Methods: A case of KPC-Kp was considered to be a patient positive for KPC-Kp with strong epidemiological plausibility of having acquired this microorganism in the affected wards and/or with genetic relationship ≥92% between KPC-Kp isolates. Active surveillance cultures (ASCs) and real-time polymerase chain reaction were used for the detection of carbapenemase genes through rectal swab in a selected population. Molecular analysis was performed using pulsed-field gel electrophoresis at the National Reference Laboratory. Patient risk factors were collected from the electronic medical record system. Information regarding outbreak containment strategy was collected from the Infection Control Unit records. Results: Of the 16 cases, 11 (69%) were identified through active screening, representing 1.4% of the total 766 ASCs collected. The most frequent risk factors identified were previous admission (63%), antibiotic exposure in the past 6 months (50%), and immunodepression (44%). The length of stay until KPC-Kp detection was high (0-121 days, mean 35.6), as was the total length of stay (5-173 days, mean 56.6). Three patients (19%) were infected by KPC-Kp, 2 of whom died. One previously colonized patient died later because of KPC-Kp infection. Conclusions: Multifactorial strategy based on contact precautions (with patient and healthcare professional cohorts) and ASC, as well as Antibiotic Stewardship Program reinforcement, allowed to contain this KPC-Kp outbreak.

CavBench: A benchmark for protein cavity detection methods.

Extensive research has been applied to discover new techniques and methods to model protein-ligand interactions. In particular, considerable efforts focused on identifying candidate binding sites, which quite often are active sites that correspond to protein pockets or cavities. Thus, these cavities play an important role in molecular docking. However, there is no established benchmark to assess the accuracy of new cavity detection methods. In practice, each new technique is evaluated using a small set of proteins with known binding sites as ground-truth. However, studies supported by large datasets of known cavities and/or binding sites and statistical classification (i.e., false positives, false negatives, true positives, and true negatives) would yield much stronger and reliable assessments. To this end, we propose CavBench, a generic and extensible benchmark to compare different cavity detection methods relative to diverse ground truth datasets (e.g., PDBsum) using statistical classification methods.

Geometric Detection Algorithms for Cavities on Protein Surfaces in Molecular Graphics: A Survey.

Detecting and analyzing protein cavities provides significant information about active sites for biological processes (e.g., protein-protein or protein-ligand binding) in molecular graphics and modeling. Using the three-dimensional structure of a given protein (i.e., atom types and their locations in 3D) as retrieved from a PDB (Protein Data Bank) file, it is now computationally viable to determine a description of these cavities. Such cavities correspond to pockets, clefts, invaginations, voids, tunnels, channels, and grooves on the surface of a given protein. In this work, we survey the literature on protein cavity computation and classify algorithmic approaches into three categories: evolution-based, energy-based, and geometry-based. Our survey focuses on geometric algorithms, whose taxonomy is extended to include not only sphere-, grid-, and tessellation-based methods, but also surface-based, hybrid geometric, consensus, and time-varying methods. Finally, we detail those techniques that have been customized for GPU (Graphics Processing Unit) computing.

Computational 3D Assembling Methods for DNA: A Survey.

DNA encodes the genetic information of most living beings, except viruses that use RNA. Unlike other types of molecules, DNA is not usually described by its atomic structure being instead usually described by its base-pair sequence, i.e., the textual sequence of its subsidiary molecules known as nucleotides ( adenine (A), cytosine (C), guanine (G), and thymine (T)). The three-dimensional assembling of DNA molecules based on its base-pair sequence has been, for decades, a topic of interest for many research groups all over the world. In this paper, we survey the major methods found in the literature to assemble and visualize DNA molecules from their base-pair sequences. We divided these methods into three categories: predictive methods, adaptive methods, and thermodynamic methods . Predictive methods aim to predict a conformation of the DNA from its base pair sequence, while the goal of adaptive methods is to assemble DNA base-pairs sequences along previously known conformations, as needed in scenarios such as DNA Monte Carlo simulations. Unlike these two geometric methods, thermodynamic methods are energy-based and aim to predict secondary structural motifs of DNA in cases where hydrogen bonds between base pairs might be broken because of temperature changes. We also present the major software tools that implements predictive, adaptive, and thermodynamic methods.

Habilidades motoras de cadeirantes influenciadas pelo controle de tronco / Motor skills wheelchairs influenced by trunk control

O objetivo deste estudo foi analisar a efetividade de um protocolo de treinamento de estabilização segmentar lombar (ESL) no controle de tronco e nas habilidades em cadeira de rodas (CR) em indivíduos paraplégicos. A amostra foi composta por 5 homens (31,2±12,9 anos) com lesão medular abaixo de T6. O deslocamento total (DT) e as amplitudes ântero-posterior (AP) e médio-lateral (ML) do centro de pressão (CP) foram analisados por meio de uma plataforma de força, em duas posições de teste (mãos no joelho e braços cruzados) e as habilidades na cadeira de rodas foram analisadas pelo Wheelchair Skills Test (WST), pré e pós protocolo de treinamento de ESL. A análise estatística foi realizada no software SPSS (15.0), utilizando o teste ANOVA para α ≤ 0,05. Na comparação pré e pós-treino, houve redução significativa do deslocamento total do CP na posição sentada com mãos nos joelhos (P<0,01) e braços cruzados (P<0,01). Não se observou mudança nas habilidades com CR do WST entre as avaliações pré e pós treinamento em nenhum dos níveis estudados. O protocolo de treinamento de ESL proposto foi efetivo para a melhora do controle de tronco, mas não modificou as habilidades no manejo de cadeira de rodas em indivíduos paraplégicos.

The aim of this study was to analyze the effectiveness of a training protocol for Lumbar Segmental Stabilization (LSS) on trunk control and skills on wheelchair management (WC) in paraplegic individuals. The sample consisted of 5 men (31.2±12.9 years) with spinal cord injury below T6. The total displacement (TD) and the anteroposterior (AP) and medial-lateral (ML) amplitudes of center of pressure (COP) were analyzed using a force platform in two test positions (hands on knees and crossover arms). Skills in the wheelchair were analyzed by the Wheelchair Skills Test (WST), pre and post LSS training protocol. The statistical analysis was performed with SPSS (15.0) using an ANOVA test (α≤0.05). In comparison pre- and post-training, there was significant reduction in the TD of the CP in the sitting position with hands on knees (P<0.01) and crossed arms on chest (P<0.01). There was no change in skills (as measured by the WST) between pre- and post-training in any of the levels studied. The LSS training protocol proposed was effective for improving trunk control, but did not change the skills for wheelchair management in paraplegic individuals.

Efeitos da estabilização segmentar lombar no equilíbrio de tronco em paraplégicos / Effects of lumbar segmental stabilization in paraplegics' trunk balance

Objetivo: Analisar o efeito da técnica de estabilização segmentar no equilíbrio de tronco (ET) em paraplégicos. Material e Métodos: Participaram do estudo cinco sujeitos, do sexo masculino (31,2 ± 12,93 anos) com diagnóstico de lesão medular (T6 a L1) e submetidos à avaliação eletromiográfica dos músculos multífido lombar (ML) e transverso do abdômen (TrA) e do ET, em duas posições (mãos nos joelhos e braços cruzados), antes e após quatro semanas de treino de estabilização segmentar lombar (ESL). As comparações das médias da Root Mean Square (RMS) do sinal EMGs e do deslocamento do centro de pressão (CP), pré e pós-treino foram realizadas no Software SPSS (15.0), utilizando os testes t Student e Wilcoxon, com nível de significância de 5%. Resultados: Houve diferença significativa na RMS do sinal EMGs (P=0,043) para os dois músculos analisados (ML e TrA) e também no deslocamento total do CP entre as avaliações pré e pós-treino, tanto na posição de mãos nos joelhos (P=0,014) quanto na posição de braços cruzados (P=0,022). Conclusão: Os resultados mostram que o protocolo de ESL empregado foi eficiente na melhora no equilíbrio do tronco e na ativação dos músculos ML e TrA.

Objective: To analyze the effect of segmental stabilization on paraplegics' trunk balance. Material and Methods: This study included five male subjects (31.2 ± 12.93 years) diagnosed with spinal cord injury (T6 to L1). They were submitted to electromyographic evaluation of the lumbar multifidus (LM) and transversus abdominus (TrA) muscles, in addition to TB assessment in two positions (hands on knees and crossed arms), before and after four weeks of lumbar segmental stabilization (LSS) training. The comparisons of the Root Mean Square (RMS) of the EMGs signal and of the displacement of the pressure center (PC) pre- and post-training were conducted on SPSS software (15.0). The Student and Wilcoxon tests were used, with significance level of 5%. Results: There was significant difference in the RMS of the EMGs signal (p=0.043) for the two muscles analyzed (LM and TrA) and in the total displacement of the PC between pre- and post-training, both in the hands on knees position (p=0.014) and in the crossed arms position (p=0.022). Conclusion: The findings showed that the LSS protocol was efficient in improving the balance of the trunk and the activation of the TrA and LM muscles.