Several research projects in this proposal focus on environmental pollutants that bind to specific protein receptors and impact regulatory pathways, resulting in developmental and reproductive abnormalities. The bioinformatics and molecular modeling research support core will facilitate the use of modern computational tools to study these interactions at the molecular level. Software and expert help is offered in four different areas: (1) bioinformatics, (2) molecular modeling and visualization, (3) protein structure prediction by homology modeling, and (4) analysis of receptor-ligand interactions. The bioinformatics tools include screening databases for similar sequences, aligning sequences for evolutionary inferences, and constructing evolutionary trees. The core will provide a variety of molecular modeling and visualization tools for the analysis of DNA and protein structures. In particular, software packages and modeling expertise will be provided for elucidating the tertiary structure of proteins that exhibit a reasonable degree of homology (at least 30% sequence identity) to a protein with known 3D structure, thereby providing potentially very valuable structural information in several research projects Protein structures, obtained either experimentally or by homology modeling, will be used to construct putative models of complexes with ligands of interest. Docking algorithms are provided for small organic molecules, flexible peptides, and proteins The analysis of predicted receptor-ligand interactions will suggest further experiments, and may help to elucidate the mechanism of action of the ligands studied. The core will have programs to search entire databases of organic molecules for ligands with high affinity for a given receptor.
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