CCM Colloquium: Short talks by Tanya Wang, Julian Giraldo Barreto and David Silva Sanchez

Wednesday Nov 10, 2021, 10:00 AM → 11:30 AM America/New_York

Presenter 1: Tanya Wang, Joint work with Alex Barnett and Manas Rachh 

Title: Discrete Molecule Detection in 2D

Abstract: Template matching applied to (cryo-EM)-basedtomograms aims to determine whether certain proteins are present inexperimental (projected) images by comparison with computed protein templates.Our toy model constructs random 2D molecules with noise, randomly translate androtate the molecules, and make corresponding 1D projections onto discretepixels. We implement several approaches to detect a single molecule (signal)and determine its location and orientation by template-matching the (noiseless)1D projections. We compare a square molecule and a high-aspect-ratio moleculeby computing and visualizing the accuracy and precision of detection for eachmolecule accordingly. Some of the results can be proved analytically

Presenter 2: Julian David Giraldo Barreto

Title: Free-energy profiles from cryoEM particles and path optimization.

Abstract: Cryo-electron microscopy (or cryo-EM) is an experimental technique that measures single-particle projections of biomolecules. Although single-particle cryo-EM is widely used for 3D reconstruction, it has the potential to provide information about a biomolecule’s conformational variability, which leads to the underlying free-energy landscape of the system. However, cryo-EM images are challenging to analyze due to their low signal-to-noise ratio. To address these issues, we developed the cryo-BIFE method. This method uses a path collective variable together with a Bayesian approach to infer free-energy profiles and their uncertainties from cryo-EM raw images. We apply the method over a diverse set of synthetic and real systems. As a second part of the talk, a path optimization method to select the lowest free-energy path will be outlined. I will present simple toy models that show where the assumptions and theory breakdown. Overall, we expect our tool for extracting free-energy profiles from cryo-EM images to enable a more complete characterization of the thermodynamic ensemble of biomolecules.

Presenter 3: David Silva Sanchez

Title: Biasing Molecular Dynamics simulations with 2-D Cryo-EM Images

Abstract: In this talk, I will present how 2-D cryo-EM images can be used to bias molecular dynamics simulations. First, I will show how to calculate a cryo-EM image from an atomic model, and how to compare the calculated image with experimental data to create a biasing force. Then, I will show how the biasing force can be used to drive the system towards the conformation represented by the images using gradient descent and molecular dynamics simulations.

If you would like to attend, please email crampersad@flatironinstitute.org for the Zoom link.