Molecular models of NS3 protease variants of the Hepatitis C virus

Background: Hepatitis C virus (HCV) currently infects approximately three percent of the world population. In view of the lack of vaccines against HCV, there is an urgent need for an efficient treatment of the disease by an effective antiviral drug. Rational drug design has not been the primary way for discovering major therapeutics. Nevertheless, there are reports of success in the development of inhibitor using a structure-based approach. One of the possible targets for drug development against HCV is the NS3 protease variants. Based on the three-dimensional structure of these variants we expect to identify new NS3 protease inhibitors. In order to speed up the modeling process all NS3 protease variant models were generated in a Beowulf cluster. The potential of the structural bioinformatics for development of new antiviral drugs is discussed.Results: the atomic coordinates of crystallographic structure 1CU1 and 1DY9 were used as starting model for modeling of the NS3 protease variant structures. The NS3 protease variant structures are composed of six subdomains, which occur in sequence along the polypeptide chain. The protease domain exhibits the dual beta-barrel fold that is common among members of the chymotrypsin serine protease family. The helicase domain contains two structurally related beta-alpha-beta subdomains and a third subdomain of seven helices and three short beta strands. The latter domain is usually referred to as the helicase alpha-helical subdomain. The rmsd value of bond lengths and bond angles, the average G-factor and Verify 3D values are presented for NS3 protease variant structures.Conclusions: This project increases the certainty that homology modeling is an useful tool in structural biology and that it can be very valuable in annotating genome sequence information and contributing to structural and functional genomics from virus. The structural models will be used to guide future efforts in the structure-based drug design of a new generation of NS3 protease variants inhibitors. All models in the database are publicly accessible via our interactive website, providing us with large amount of structural models for use in protein-ligand docking analysis.

Parmodel: a web server for automated comparative modeling of proteins

Parmodel is a web server for automated comparative modeling and evaluation of protein structures. The aim of this tool is to help inexperienced users to perform modeling, assessment, visualization, and optimization of protein models as well as crystallographers to evaluate structures solved experimentally. It is subdivided in four modules: Parmodel Modeling, Parmodel Assessment, Parmodel Visualization, and Parmodel Optimization. The main module is the Parmodel Modeling that allows the building of several models ford a same protein in a reduced time, through the distribution of modeling processes on a Beowulf cluster. Parmodel automates and integrates the main softwares used in comparative modeling as MODELLER, Whatcheck, Procheck, Raster3D, Molscript, and Gromacs. This web server is freely accessible at http://www.biocristalografia.df.ibilce.unesp.br/tools/parmodel. (C) 2004 Elsevier B.V. All rights reserved.

Avaliação de Desempenho de Aplicações Paralelas Utilizando MPI e PETSc

This work presents a study about the use of standards and directions on parallel programming in distributed systems, using the MPI standard and PETSc toolkit, performing an analysis of their performances over certain mathematic operations involving matrices. The concepts are used to develop applications to solve problems involving Principal Components Analysis (PCA), which are executed in a Beowulf cluster. The results are compared to the ones of an analogous application with sequencial execution, and then it is analized if there was any performance boost on the parallel application