RESUMO
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 for 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 .
Assuntos
Algoritmos , Internet , Modelos Químicos , Modelos Moleculares , Proteínas/química , Análise de Sequência de Proteína/métodos , Software , Simulação por Computador , Sistemas de Gerenciamento de Base de Dados , Bases de Dados de Proteínas , Armazenamento e Recuperação da Informação/métodos , Conformação Proteica , Proteínas/classificação , Alinhamento de Sequência/métodos , Interface Usuário-ComputadorRESUMO
The parasite Schistosoma mansoni lacks the de novo pathway for purine biosynthesis and depends on salvage pathways for its purine requirements. Schistosomiasis is endemic in 76 countries and territories and amongst the parasitic diseases ranks second after malaria in terms of social and economic impact and public health importance. The PNP is an attractive target for drug design and it has been submitted to extensive structure-based design. The atomic coordinates of the complex of human PNP with inosine were used as template for starting the modeling of PNP from S. mansoni complexed with inosine. Here we describe the model for the complex SmPNP-inosine and correlate the structure with differences in the affinity for inosine presented by human and S. mansoni PNPs.
Assuntos
Inosina/química , Modelos Químicos , Modelos Moleculares , Purina-Núcleosídeo Fosforilase/química , Schistosoma mansoni/enzimologia , Análise de Sequência de Proteína/métodos , Sequência de Aminoácidos , Animais , Sítios de Ligação , Biologia Computacional/métodos , Simulação por Computador , Ativação Enzimática , Humanos , Dados de Sequência Molecular , Ligação Proteica , Conformação Proteica , Estrutura Secundária de ProteínaRESUMO
Here is described a structural model for the binary complex CDK5-roscovitine. Roscovitine has been shown to potently inhibit cyclin-dependent kinases 1, 2 and 5 (CDK1, 2, and 5), and the structure of CDK2 complexed with roscovitine has been reported; however, no structural data are available for complexes of CDK5 with inhibitors. The structural model indicates that roscovitine strongly binds to the ATP-binding pocket of CDK5 and structural comparison of the CDK2-roscovitine complex correlates the structural differences with differences in inhibition of these CDKs by this inhibitor. This structure opens the possibility of testing new inhibitor families, in addition to new substituents for the already known lead structures of adenine derivatives.