Comparative modelling and in-silico drug designing
11 Apr 2013-pp 600-605
TL;DR: 3-D structures of Harpin protein, Single-stranded DNA binding protein, and R2.LlaJI (Campylobacter conisus 13826) has been modelled and can serve as pharmacophores for the designing of potential drugs against diseases.
Abstract: In this study, 3-D structures of Harpin protein (Pectobacterium carotovorum), Single-stranded DNA binding protein (Pseudomonas aeruginosa), and R2.LlaJI (Campylobacter conisus 13826) has been modelled. For modelling, template selection is done by BLASTp search. For target template alignment, ClustalW server is used and then comparative modelling was done by Modeller9.1O. Validation of models was done by PROCHECK and ProSA-web. After this, the best model out of all, for each of the proteins was selected and their active sites was obtained using CASTp. Core drug was selected by literature search and different leads were designed for the target proteins using MARVIN SKETCH. Docking was done by HEX5.1 followed by AutoDock4. The best lead selected after this study can serve as pharmacophores for the designing of potential drugs against diseases.
TL;DR: This new version of CASTp includes annotated functional information of specific residues on the protein structure that is derived from the Protein Data Bank, Swiss-Prot, as well as Online Mendelian Inheritance in Man.
Abstract: Cavities on a proteins surface as well as specific amino acid positioning within it create the physicochemical properties needed for a protein to perform its function. CASTp (http://cast.engr.uic.edu) is an online tool that locates and measures pockets and voids on 3D protein structures. This new version of CASTp includes annotated functional information of specific residues on the protein structure. The annotations are derived from the Protein Data Bank (PDB), Swiss-Prot, as well as Online Mendelian Inheritance in Man (OMIM), the latter contains information on the variant single nucleotide polymorphisms (SNPs) that are known to cause disease. These annotated residues are mapped to surface pockets, interior voids or other regions of the PDB structures. We use a semi-global pair-wise sequence alignment method to obtain sequence mapping between entries in Swiss-Prot, OMIM and entries in PDB. The updated CASTp web server can be used to study surface features, functional regions and specific roles of key residues of proteins.
TL;DR: Computed Atlas of Surface Topography of proteins (CASTp) provides an online resource for locating, delineating and measuring concave surface regions on three-dimensional structures of proteins, including pockets located on protein surfaces and voids buried in the interior of proteins.
Abstract: Computed Atlas of Surface Topography of proteins (CASTp) provides an online resource for locating, delineating and measuring concave surface regions on three-dimensional structures of proteins. These include pockets located on protein surfaces and voids buried in the interior of proteins. The measurement includes the area and volume of pocket or void by solvent accessible surface model (Richards' surface) and by molecular surface model (Connolly's surface), all calculated analytically. CASTp can be used to study surface features and functional regions of proteins. CASTp includes a graphical user interface, flexible interactive visualization, as well as on-the-fly calculation for user uploaded structures. CASTp is updated daily and can be accessed at http://cast.engr.uic.edu.
TL;DR: This article describes and reviews the efforts using Hex 3.1 to predict the docking modes of the seven target protein–protein complexes presented in the CAPRI (Critical Assessment of Predicted Interactions) blind docking trial, and describes several enhancements to the original spherical polar Fourier docking correlation algorithm.
Abstract: This article describes and reviews our efforts using Hex 3.1 to predict the docking modes of the seven target protein-protein complexes presented in the CAPRI (Critical Assessment of Predicted Interactions) blind docking trial. For each target, the structure of at least one of the docking partners was given in its unbound form, and several of the targets involved large multimeric structures (e.g., Lactobacillus HPr kinase, hemagglutinin, bovine rotavirus VP6). Here we describe several enhancements to our original spherical polar Fourier docking correlation algorithm. For example, a novel surface sphere smothering algorithm is introduced to generate multiple local coordinate systems around the surface of a large receptor molecule, which may be used to define a small number of initial ligand-docking orientations distributed over the receptor surface. High-resolution spherical polar docking correlations are performed over the resulting receptor surface patches, and candidate docking solutions are refined by using a novel soft molecular mechanics energy minimization procedure. Overall, this approach identified two good solutions at rank 5 or less for two of the seven CAPRI complexes. Subsequent analysis of our results shows that Hex 3.1 is able to place good solutions within a list of
TL;DR: A number of compounds are reported which are capable of restoring the phenotype to a HSL negative mutant but at higher concentrations than HSL.
Abstract: N-(3-Oxohexanoyl)-L-homoserine lactone (HSL) (I) is the autoregulator controlling carbapenem antibiotic biosynthesis in Erwinia carotovora ATCC 39048. The chemical synthesis and biological evaluation of analogues of HSL are described. These include alterations of chirality, side-chain modifications, ring size and ring hetero atom. A number of compounds are reported which are capable of restoring the phenotype to a HSL negative mutant but at higher concentrations than HSL. A-factor, the autoregulator of streptomycin biosynthesis in Streptomyces griseus, was not active as an inducer of carbapenem biosynthesis in E. carotovora.
TL;DR: Synthesis of seven new indolenyl sulfonamides, prepared by the condensation reaction of indole-3-carboxaldehyde with different sulfon amides, showed significant antibacterial activity whereas most of the compounds displayed good antifungal activity.