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

, Bason Clancy

, Joshua Salafsky

, Andrej Sali

University of California, San Francisco, San Francisco, CA, USA,

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.