PocketAlign A Novel Algorithm for Aligning Binding Sites in Protein Structures

A fundamental task in bioinformatics involves a transfer of knowledge from one protein molecule onto another by way of recognizing similarities. Such similarities are obtained at different levels, that of sequence, whole fold, or important substructures. Comparison of binding sites is important to understand functional similarities among the proteins and also to understand drug cross-reactivities. Current methods in literature have their own merits and demerits, warranting exploration of newer concepts and algorithms, especially for large-scale comparisons and for obtaining accurate residue-wise mappings. Here, we report the development of a new algorithm, PocketAlign, for obtaining structural superpositions of binding sites. The software is available as a web-service at http://proline.physicslisc.emetin/pocketalign/. The algorithm encodes shape descriptors in the form of geometric perspectives, supplemented by chemical group classification. The shape descriptor considers several perspectives with each residue as the focus and captures relative distribution of residues around it in a given site. Residue-wise pairings are computed by comparing the set of perspectives of the first site with that of the second, followed by a greedy approach that incrementally combines residue pairings into a mapping. The mappings in different frames are then evaluated by different metrics encoding the extent of alignment of individual geometric perspectives. Different initial seed alignments are computed, each subsequently extended by detecting consequential atomic alignments in a three-dimensional grid, and the best 500 stored in a database. Alignments are then ranked, and the top scoring alignments reported, which are then streamed into Pymol for visualization and analyses. The method is validated for accuracy and sensitivity and benchmarked against existing methods. An advantage of PocketAlign, as compared to some of the existing tools available for binding site comparison in literature, is that it explores different schemes for identifying an alignment thus has a better potential to capture similarities in ligand recognition abilities. PocketAlign, by finding a detailed alignment of a pair of sites, provides insights as to why two sites are similar and which set of residues and atoms contribute to the similarity.

Fermion Electric Dipole Moments in R-parity violating Supersymmetry

In this talk I discuss some aspects of the study of electric dipole moments (EDMs) of the fermions, in the context of R-parity violating (\rpv) Supersymmetry (SUSY). I will start with a brief general discussion of how dipole moments, in general, serve as a probe of physics beyond the Standard Model (SM) and an even briefer summary of \rpv SUSY. I will follow by discussing a general method of analysis for obtaining the leading fermion mass dependence of the dipole moments and present its application to \rpv SUSY case. Then I will summarise the constraints that the analysis of $e,n$ and $Hg$ EDMs provide for the case of trilinear \rpv SUSY couplings and make a few comments on the case of bilinear \rpv, where the general method of analysis proposed by us does not work.

Is diatom earth a collapsible material?

Analysis of compressibility data of diatom earth and Ariake clay of similar water holding capacities has been made in this paper. Analysis suggests that in the case of clays with sheet minerals such as in Ariake clays, due to compression, cluster growth takes place, whereas with diatom earth the breakdown of cluster accounts for bilinear compression characteristics. It has been hypothesized that the interactive void ratio in the case of diatom earth is likely to be far smaller than that in the case of Ariake clay where most of the pore water is herd by micropores enclosed by clay particle clusters. In a way diatom earth reflects the behaviour of clay of very law physico-chemical potential with far reduced collapse potential. Even the compressibility at higher stress range both in undisturbed and remolded states are likely to be due to breakdown of clusters with little contribution from the physico - chemical potential. Diatom earth is not a collapsible material at stress levels of engineering interest despite the in -situ water content is at par or even higher than soft sensitive Ariake clay with comparatively low cementation consequently with pronounced collapsible potential.

Residual strength evaluation of concrete structural components under fatigue loading

This paper presents methodologies for residual strength evaluation of concrete structural components using linear elastic and nonlinear fracture mechanics principles. The effect of cohesive forces due to aggregate bridging has been represented mathematically by employing tension softening models. Various tension softening models such as linear, bilinear, trilinear, exponential and power curve have been described with appropriate expressions. These models have been validated by predicting the remaining life of concrete structural components and comparing with the corresponding experimental values available in the literature. It is observed that the predicted remaining life by using power model and modified bi-linear model is in good agreement with the corresponding experimental values. Residual strength has also been predicted using these tension softening models and observed that the predicted residual strength is in good agreement with the corresponding analytical values in the literature. In general, it is observed that the variation of predicted residual moment with the chosen tension softening model follows the similar trend as in the case of remaining life. Linear model predicts large residual moments followed by trilinear, bilinear and power models.

Implication of a Higgs boson at 125 GeV within the stochastic superspace framework

We revisit the issue of considering stochasticity of Grassmannian coordinates in N = 1 superspace, which was analyzed previously by Kobakhidze et al. In this stochastic supersymmetry (SUSY) framework, the soft SUSY breaking terms of the minimal supersymmetric Standard Model (MSSM) such as the bilinear Higgs mixing, trilinear coupling, as well as the gaugino mass parameters are all proportional to a single mass parameter xi, a measure of supersymmetry breaking arising out of stochasticity. While a nonvanishing trilinear coupling at the high scale is a natural outcome of the framework, a favorable signature for obtaining the lighter Higgs boson mass m(h) at 125 GeV, the model produces tachyonic sleptons or staus turning to be too light. The previous analyses took Lambda, the scale at which input parameters are given, to be larger than the gauge coupling unification scale M-G in order to generate acceptable scalar masses radiatively at the electroweak scale. Still, this was inadequate for obtaining m(h) at 125 GeV. We find that Higgs at 125 GeV is highly achievable, provided we are ready to accommodate a nonvanishing scalar mass soft SUSY breaking term similar to what is done in minimal anomaly mediated SUSY breaking (AMSB) in contrast to a pure AMSB setup. Thus, the model can easily accommodate Higgs data, LHC limits of squark masses, WMAP data for dark matter relic density, flavor physics constraints, and XENON100 data. In contrast to the previous analyses, we consider Lambda = M-G, thus avoiding any ambiguities of a post-grand unified theory physics. The idea of stochastic superspace can easily be generalized to various scenarios beyond the MSSM. DOI: 10.1103/PhysRevD.87.035022

PocketMatch (version 2.0): A parallel algorithm for the detection of structural similarities between protein ligand binding-sites

Knowledge of protein-ligand interactions is essential to understand several biological processes and important for applications ranging from understanding protein function to drug discovery and protein engineering. Here, we describe an algorithm for the comparison of three-dimensional ligand-binding sites in protein structures. A previously described algorithm, PocketMatch (version 1.0) is optimised, expanded, and MPI-enabled for parallel execution. PocketMatch (version 2.0) rapidly quantifies binding-site similarity based on structural descriptors such as residue nature and interatomic distances. Atomic-scale alignments may also be obtained from amino acid residue pairings generated. It allows an end-user to compute database-wide, all-to-all comparisons in a matter of hours. The use of our algorithm on a sample dataset, performance-analysis, and annotated source code is also included.

Fault Attacks on Pairing-Based Protocols Revisited

Several papers have studied fault attacks on computing a pairing value e(P, Q), where P is a public point and Q is a secret point. In this paper, we observe that these attacks are in fact effective only on a small number of pairing-based protocols, and that too only when the protocols are implemented with specific symmetric pairings. We demonstrate the effectiveness of the fault attacks on a public-key encryption scheme, an identity-based encryption scheme, and an oblivious transfer protocol when implemented with a symmetric pairing derived from a supersingular elliptic curve with embedding degree 2.

Efficient Protocol for Authenticated Email Search

Executing authenticated computation on outsourced data is currently an area of major interest in cryptology. Large databases are being outsourced to untrusted servers without appreciable verification mechanisms. As adversarial server could produce erroneous output, clients should not trust the server's response blindly. Primitive set operations like union, set difference, intersection etc. can be invoked on outsourced data in different concrete settings and should be verifiable by the client. One such interesting adaptation is to authenticate email search result where the untrusted mail server has to provide a proof along with the search result. Recently Ohrimenko et al. proposed a scheme for authenticating email search. We suggest significant improvements over their proposal in terms of client computation and communication resources by properly recasting it in two-party settings. In contrast to Ohrimenko et al. we are able to make the number of bilinear pairing evaluation, the costliest operation in verification procedure, independent of the result set cardinality for union operation. We also provide an analytical comparison of our scheme with their proposal which is further corroborated through experiments.

Tensile and compressive deformation of a short-glass-fiber-reinforced liquid-crystalline polymer

Results of tensile and compression tests on a short-glass-fiber-reinforced thermotropic liquid crystalline polymer are presented. The effect of strain rate on the compression stress-strain characteristics has been investigated over a wide range of strain rates epsilon between 10(-4) and 350 s-1. The low-strain-rate tests were conducted using a screw-driven universal tensile tester, while the high-strain-rate tests were carried out using the split Hopkinson pressure bar technique. The compression modulus was shown to vary with log10 (epsilon) in a bilinear manner. The compression modulus is insensitive to strain rate in the low-strain-rate regime (epsilon = 10(-4) - 10(-2) s-1), but it increases more rapidly with epsilon at higher epsilon. The compression strength changes linearly with log10 (epsilon) over the entire strain-rate range. The fracture surfaces were examined by scanning electron microscopy.

Range of validity of the method of averaging

Sufficient conditions are derived for the validity of approximate periodic solutions of a class of second order ordinary nonlinear differential equations. An approximate solution is defined to be valid if an exact solution exists in a neighborhood of the approximation.

Two classes of validity criteria are developed. Existence is obtained using the contraction mapping principle in one case, and the Schauder-Leray fixed point theorem in the other. Both classes of validity criteria make use of symmetry properties of periodic functions, and both classes yield an upper bound on a norm of the difference between the approximate and exact solution. This bound is used in a procedure which establishes sufficient stability conditions for the approximated solution.

Application to a system with piecewise linear restoring force (bilinear system) reveals that the approximate solution obtained by the method of averaging is valid away from regions where the response exhibits vertical tangents. A narrow instability region is obtained near one-half the natural frequency of the equivalent linear system. Sufficient conditions for the validity of resonant solutions are also derived, and two term harmonic balance approximate solutions which exhibit ultraharmonic and subharmonic resonances are studied.

Applications of plasticity theory to selected problems in soil mechanics

Two topics in plane strain perfect plasticity are studied using the method of characteristics. The first is the steady-state indentation of an infinite medium by either a rigid wedge having a triangular cross section or a smooth plate inclined to the direction of motion. Solutions are exact and results include deformation patterns and forces of resistance; the latter are also applicable for the case of incipient failure. Experiments on sharp wedges in clay, where forces and deformations are recorded, showed a good agreement with the mechanism of cutting assumed by the theory; on the other hand the indentation process for blunt wedges transforms into that of compression with a rigid part of clay moving with the wedge. Finite element solutions, for a bilinear material model, were obtained to establish a correspondence between the response of the plane strain wedge and its axi-symmetric counterpart, the cone. Results of the study afford a better understanding of the process of indentation of soils by penetrometers and piles as well as the mechanism of failure of deep foundations (piles and anchor plates).

The second topic concerns the plane strain steady-state free rolling of a rigid roller on clays. The problem is solved approximately for small loads by getting the exact solution of two problems that encompass the one of interest; the first is a steady-state with a geometry that approximates the one of the roller and the second is an instantaneous solution of the rolling process but is not a steady-state. Deformations and rolling resistance are derived. When compared with existing empirical formulae the latter was found to agree closely.

Avaliação de ligações K e T entre perfis estruturais tubulares circulares.

O difundido uso de perfis estruturais tubulares, principalmente devido às vantagens associadas ao comportamento estrutural e estético, levou a uma intensa utilização nos países da Europa, Sudeste Asiático, América do Norte e na Austrália. Países como Canadá, Inglaterra, Alemanha e Holanda fazem uso intensivo dessas estruturas e contam com uma produção corrente, industrializada e contínua com alto grau de desenvolvimento tecnológico. O aumento da oferta deste tipo de perfis, aliado a recentes pesquisas nesta área, leva o Brasil a se inserir neste cenário mundial. Entretanto, as normas brasileiras que regem o dimensionamento destes perfis ainda não se encontram atualizadas, principalmente no que tange ao dimensionamento de ligações de perfis tubulares. Considerando esta perspectiva, este trabalho apresenta uma análise de ligações tipo K e T com perfis tubulares circulares (CHS). Propõe-se estabelecer um quadro comparativo entre as formulações analíticas de dimensionamento proposta pelo Eurocode 3 Parte 1.8, 2 edição do guia de projeto de ligações tubulares do CIDECT, projeto de norma brasileira PN 02.125.03-004 e critérios de deformação limite. Para cada um dos tipos de ligações analisadas, desenvolveu-se um modelo em elementos finitos no programa Ansys, calibrado e validado com resultados experimentais e numéricos existentes na literatura. As não-linearidades física e geométrica foram incorporadas aos modelos, a fim de se mobilizar totalmente a capacidade resistente da ligação. A não-linearidade do material foi considerada através do critério de plastificação de Von Mises através de uma lei constitutiva tensão versus deformação bilinear. A não-linearidade geométrica foi introduzida no modelo através da Formulação de Lagrange Atualizado considerando-se a previsão de grandes deformações de forma a permitir a redistribuição de carregamento na ligação após o escoamento inicial. Esta dissertação propõe ainda, a modelagem de uma treliça planar constituída de perfis tubulares, objetivando estabelecer uma comparação entre um nó isolado e um nó da treliça planar.

Avaliação de ligações soldadas de perfis tubulares em estruturas de aço através do método dos elementos finitos.

A necessidade de se obter soluções para os diversos problemas estruturais na engenharia, associado ao amplo crescimento e difusão da construção metálica fez surgir, por volta dos anos 60, os perfis tubulares. As ligações soldadas entre perfis tubulares são as ligações de maior difusão nas construções com este tipo de perfil, sendo necessário portanto, estudos mais detalhados que tornem a utilização de ligações soldadas mais seguras e otimizadas. O Eurocode 3 possui um item específico para as ligações entre perfis tubulares, em especial as ligações soldadas devido a suas particularidades. Infelizmente, a norma brasileira NBR8800 não aborda as ligações envolvendo perfis tubulares. Para a execução da análise numérica no presente trabalho, faz-se necessário uma revisão bibliográfica. Com estes resultados, foram feitas modelagens de ligações tubulares com o método dos elementos finitos de forma a otimizar os modelos a serem utilizados em uma análise paramétrica futura. Desta forma, foram desenvolvidos dois modelos numéricos, um considerando ligação tipo T entre perfis tubulares quadrados e outro para uma ligação tipo K entre perfis circulares. Estes modelos foram caracterizados através de elementos de casca com seis graus de liberdade por nó considerando-se adicionalmente o efeito de membrana. A análise não-linear realizada considerou a não-linearidade do material através do critério de plastificação de Von Mises através de uma lei constitutiva tensão versus deformação bi-linear e a não-linearidade geométrica foi atribuída através da formulação de Lagrange atualizado. Dentre as principais conclusões obtidas no presente trabalho, pode-se citar que os resultados para as ligações tipo T, o Eurocode 3, fornece resultados que precisam ser observados com cautela. Todavia, para as ligações do tipo K, os resultados numéricos mostraram-se sempre inferiores aos valores através do Eurocode 3, representando um dimensionamento a favor da segurança.

Análise de transição entre cabos coaxiais constituída por corrugações e desníveis angulares.

Esta dissertação apresenta um formalismo baseado no Método dos Elementos Finitos (MEF), adequado a análise de descontinuidades coaxiais com simetria axial, entre duas linhas coaxiais quaisquer, incluindo corrugações nos tubos internos e externos. Pelo método de Galerkin-Budnov deduz-se um operador integral bilinear, aplicado ao campo magnético, expandido em todo o domínio da estrutura, coaxial-descontinuidade-coaxial. As portas de entrada e saída da estrutura são posicionadas distantes da descontinuidade, de forma que nelas só haja o modo Transversal Eletromagnético (TEM). O campo magnético procurado e obtido pelo MEF. Os resultados encontrados; perdas de retorno, comportamento do campo magnético e as equi-fases nas portas de entrada e saída da estrutura, foram calculados e confrontados com as do Método de Casamento de Modos (MCM), com um alto grau de concordância.

Avaliação de ligações KK entre perfis tubulares em aço.

Em virtude do elevado grau de desenvolvimento da tecnologia em sua produção, a utilização de perfis tubulares é grandemente difundida em países como, por exemplo, Canadá, Inglaterra, Alemanha e Holanda. A utilização de tais perfis no Brasil era bastante restrita, limitando-se a coberturas espaciais. Atualmente, a situação do mercado brasileiro começa a se alterar em decorrência do significativo aumento da oferta de perfis tubulares estruturais. Este trabalho apresenta uma análise de ligações tipo KK com perfis tubulares circulares (CHS), com o intuito de estabelecer um quadro comparativo entre as formulações analíticas de dimensionamento proposta pelo Eurocode 3 Parte 1.8, 2 edição do guia de projeto de ligações tubulares do CIDECT, ABNT NBR 16239:2013, pelas equações propostas por Paul e Kurobane e critérios de deformação limite. A calibração de um modelo foi feita com dados numéricos e experimentais. Para cada um dos tipos de ligações analisadas, desenvolveu-se um modelo em elementos finitos no programa Ansys. As não-linearidades física e geométrica foram incorporadas aos modelos, a fim de se mobilizar totalmente a capacidade resistente da ligação. A não-linearidade do material foi considerada com o uso do critério de plastificação de Von Mises através de uma lei constitutiva tensão versus deformação bilinear. A não-linearidade geométrica foi introduzida no modelo através da Formulação de Lagrange Atualizado considerando-se a previsão de grandes deformações de forma a permitir a redistribuição de carregamento na ligação após o escoamento inicial. Foi proposto um modelo de uma treliça espacial composta por perfis tubulares de seção circular para comparar os resultados de análises de uma ligação isolada e a resposta desta mesma ligação como parte de uma treliça em escala real.