Sonya Hanson, Research Scientist and Project Leader, Structural and Molecular Biophysics Group at the Flatiron Institute Center for Computational Biology, will be on campus to give a seminar titled, "Using Molecular Simulation Toward Improved Conformational Heterogeneity Analysis in Single-Particle Cryo-EM."

Zoom link: https://gc-cuny.zoom.us/j/91032629703. Meeting ID: 910 3262 9703. Passcode: ASRC+CCNY

ABSTRACT

Cryo-electron microscopy (cryo-EM) has become the premier method for high resolution structure determination of biological macromolecules above a certain size. However, current methods average out or even discard the information available about the conformational heterogeneity of individual molecules in the 2D images, in favor of producing high resolution 3D volumes. Here we delve into progress and pitfalls toward the analysis of conformational heterogeneity of single-particle cryo-EM datasets. These methods have tremendous potential, but understanding the caveats of different methodologies is critical. We have taken two approaches to compare and contrast different methods in conformational heterogeneity analysis in cryo-EM: 1) analyzing a single experimental dataset using the variety of methods available and 2) conducting a conformational heterogeneity challenge for the cryo-EM community in which groups across the world participated using their own algorithms for extracting states and populations. For both of these projects using molecular dynamics (MD) simulations in combination with cryo-EM analysis methods proved invaluable, with the two approaches showing surprisingly similar conformational motions. In one case we used MD simulations as an orthogonal method for exploring the state space and in the other it provided a ground truth conformational ensemble with which we generated simulated cryo-EM data.