Conformational Ensembles from Experimental Data and Computer Simulations

Conformational Ensembles from Experimental Data and Computer Simulations

Poster Abstracts

2-POS Board 2 Determining the Information Content of Second Harmonic Generation Spectroscopy for Modeling Conformational Changes of Macromolecules Seth D. Axen 1 , Bason Clancy 2 , Joshua Salafsky 2 , Andrej Sali 1 . 1 University of California, San Francisco, San Francisco, CA, USA, 2 Biodesy, Inc., South San Francisco, CA, USA. When modeling conformational changes of proteins, often the structure of a single conformation or of individual domains is known or can be inferred from structures of homologous proteins. A number of structural techniques are available for modeling additional conformations in response to perturbations. However, many of these techniques suffer from limitations on the size of the system, are performed under non-physiological conditions, are difficult to perform, or are low- throughput. A promising new technique uses the nonlinear optic phenomenon Second Harmonic Generation (SHG) in a highly sensitive assay for conformational changes in proteins that informs relative orientations of structural components. In this work, a computational method is developed for modeling conformational changes of ideal rigid body systems using SHG data combined with distance restraints. By varying the relative density of simulated data and degrees of freedom of modeled systems, the relative information content of SHG data is estimated, and the experimental constraints necessary to increase this information content are determined, directing future SHG experiments.

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