Many biological molecules are flexible in solution. This can be assessed by nuclear magnetic resonance (NMR) methods. Indeed, J scalar coupling constants and nuclear Overhauser effect (NOE) data are subject to different types of averaging when conformers are present in solution. In such a case, it may not be possible to fit all observed NMR parameters with a single molecular conformation. We have developed a method, PARSE (Probability Assessment via Relaxation rates of a Structural Ensemble), which allows one to refine individual conformers contributing to the observable NMR parameters, and to estimate the probabilities of these conformers. Originally, we applied this method to study structural ensembles for DNA duplexes; presently we are applying it to a protein, omega-conotoxin M VII C, whose solution structure has been recently solved in Vladimir Basus' group at UCSF. The omega-conotoxins from sea snail inhibit voltage-sensitive Ca++ channels, and structural studies on conotoxins are geared at understanding of this process. The CGL resources are necessary for our project to analyze the potential conformers, and to communicate the results. Graphical representation of structural ensembles is a non-trivial problem. We are enjoying the assistance of the CGL staff in this task, in particular, from Eric Pettersen, who developed a number of original programs for displaying multiple conformers.
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