Search results for "Databases"
showing 10 items of 937 documents
Evaluating protein structures determined by structural genomics consortia.
2006
Structural genomics projects are providing large quantities of new 3D structural data for proteins. To monitor the quality of these data, we have developed the protein structure validation software suite (PSVS), for assessment of protein structures generated by NMR or X-ray crystallographic methods. PSVS is broadly applicable for structure quality assessment in structural biology projects. The software integrates under a single interface analyses from several widely-used structure quality evaluation tools, including PROCHECK (Laskowski et al., J Appl Crystallog 1993;26:283-291), MolProbity (Lovell et al., Proteins 2003;50:437-450), Verify3D (Luthy et al., Nature 1992;356:83-85), ProsaII (Si…
Molecular Docking approach on the Topoisomerase I inhibitors series included in the NCI anti-cancer agents mechanism database
2006
Topoisomerase I (Top1) is an essential enzyme participating to all those processes associated with separation of DNA strands. It manages superhelical tensions through the transient breakage of one strand of duplex DNA, followed by the unwinding of supercoiled DNA. Camptothecins, a class of alkaloids extracted from the wood of a Chinese tree, were found to be potent inhibitors of Topoisomerase I. The National Cancer Institute (NCI) Anti-cancer Agents Mechanism Database contains several camptothecins derivatives, classified as selective Top1 inhibitors. In this work we performed molecular docking studies on 24 camptothecin-like inhibitors present in this database (using Autodock 3.0.5). In or…
Molecular topology as novel strategy for discovery of drugs with aβ lowering and anti-aggregation dual activities for Alzheimer's disease.
2014
Background and Purpose: In this study, we demonstrate the use of Molecular topology (MT) in an Alzheimer's disease (AD) drug discovery program. MT uses and expands upon the principles governing the molecular connectivity theory of numerically characterizing molecular structures, in the present case, active anti-AD drugs/agents, using topological descriptors to build models. Topological characterization has been shown to embody sufficient molecular information to provide strong correlation to therapeutic efficacy. Experimental Approach: We used MT to include multiple bioactive properties that allows for the identification of multifunctional single agent compounds, in this case, the dual func…
Heterogeneity at the HLA-DRB1 locus and risk for multiple sclerosis.
2006
Variation in major histocompatibility complex genes on chromosome 6p21.3, specifically the human leukocyte antigen HLA-DR2 or DRB1*1501-DQB1*0602 extended haplotype, confers risk for multiple sclerosis (MS). Previous studies of DRB1 variation and both MS susceptibility and phenotypic expression have lacked statistical power to detect modest genotypic influences, and have demonstrated conflicting results. Results derived from analyses of 1339 MS families indicate DRB1 variation influences MS susceptibility in a complex manner. DRB1*15 was strongly associated in families (P=7.8x10(-31)), and a dominant DRB1*15 dose effect was confirmed (OR=7.5, 95% CI=4.4-13.0, P<0.0001). A modest dose effect…
DesMol2, an Effective Tool for the Construction of Molecular Libraries and Its Application to QSAR Using Molecular Topology
2019
A web application, DesMol2, which offers two main functionalities, is presented: the construction of molecular libraries and the calculation of topological indices. These functionalities are explained through a practical example of research of active molecules to the formylpeptide receptor (FPR), a receptor associated with chronic inflammation in systemic amyloidosis and Alzheimer&rsquo
In-silico screening of new potential Bcl-2/Bcl-xl inhibitors as apoptosis modulators
2008
One of the major problems in the fight against cancer is drug-resistance, which, at a molecular level, can be acquired through mutations able to deactivate apoptosis. In particular, proteins in the Bcl-2 family are central regulators of programmed cell death, and members that inhibit apoptosis, such as Bcl-xl and Bcl-2, are overexpressed in many tumours. The development of new inhibitors of these proteins as potential anticancer therapeutics represents a new frontier. In this work, we carried out an in-silico screening of compounds from a free database of more than 2 million structures (ZINC database), which allowed us to identify 17 sulfonamide derivatives as new potential inhibitors; thes…
The Protein Structure Context of PolyQ Regions.
2016
Proteins containing glutamine repeats (polyQ) are known to be structurally unstable. Abnormal expansion of polyQ in some proteins exceeding a certain threshold leads to neurodegenerative disease, a symptom of which are protein aggregates. This has led to extensive research of the structure of polyQ stretches. However, the accumulation of contradictory results suggests that protein context might be of importance. Here we aimed to evaluate the structural context of polyQ regions in proteins by analysing the secondary structure of polyQ proteins and their homologs. The results revealed that the secondary structure in polyQ vicinity is predominantly random coil or helix. Importantly, the region…
Quality assessment of protein NMR structures.
2013
Biomolecular NMR structures are now routinely used in biology, chemistry, and bioinformatics. Methods and metrics for assessing the accuracy and precision of protein NMR structures are beginning to be standardized across the biological NMR community. These include both knowledge-based assessment metrics, parameterized from the database of protein structures, and model versus data assessment metrics. On line servers are available that provide comprehensive protein structure quality assessment reports, and efforts are in progress by the world-wide Protein Data Bank (wwPDB) to develop a biomolecular NMR structure quality assessment pipeline as part of the structure deposition process. These qu…
String kernels and high-quality data set for improved prediction of kinked helices in α-helical membrane proteins.
2011
The reasons for distortions from optimal α-helical geometry are widely unknown, but their influences on structural changes of proteins are significant. Hence, their prediction is a crucial problem in structural bioinformatics. For the particular case of kink prediction, we generated a data set of 132 membrane proteins containing 1014 manually labeled helices and examined the environment of kinks. Our sequence analysis confirms the great relevance of proline and reveals disproportionately high occurrences of glycine and serine at kink positions. The structural analysis shows significantly different solvent accessible surface area mean values for kinked and nonkinked helices. More important, …
Exploiting a list of protein sequences
2007
Abstract: We describe a software program to help exploit a database of aligned protein sequences. In addition to the classical lists of sequences, a graphical representation is used to get a better overview of the information. As natural parameters, the type of amino acid and sequence position are used. Various plots or 3D representations are then updated. Examples are shown based on globin sequences from various species and on the abnormal human hemoglobins. The software should be of interest to protein engineers who need to know what variants are already known.