This seminar forms part of the AI3SD and RSC-CICAG AI4Proteins Series. This series is sponsored by Arctoris and Schrödinger.

This video is the second talk in the Protein Structure Prediction Conference.

So you predicted a protein structure – What now? – Dr Thomas Steinbrecher

Abstract: Recent advances in technologies like cryoEM structure resolution and protein de novo folding prediction have resulted in a wealth of macromolecular structures that have not been resolved to the level of detail a high-resolution X-ray crystal structure could provide. Taking full advantage of these structures for rational drug design would benefit from additional validation and refinement. In this presentation, we investigate if computational refinement and structure-based modeling methods can be utilized to generate reliable complex poses. We present a solution to the induced fit docking problem for protein−ligand binding by combining ligand-based pharmacophore docking, rigid receptor docking, and protein structure prediction with explicit solvent molecular dynamics simulations. This methodology succeeded in determining protein−ligand binding modes with a root-mean-square deviation within 2.5 Å compared to experiment in over 90% of cross-docking cases in our testing. Applications of the predicted ligand-receptor structure in free energy perturbation calculations for additional validation is demonstrated.

Bio: Thomas Steinbrecher studied Chemistry at the University of Freiburg in Germany and earned a diploma with distinction in Physical Chemistry. He completed a Ph.D. thesis on “Computer Simulations of Protein-Ligand Interactions” in 2005. He joined the developer team of the Amber MD package as a Postdoc at the Scripps Research Institute in San Diego and Rutgers University in New Jersey. The work focus was on efficient free energy calculation methods and QM/MM simulations of charge transfer. After returning to Germany in 2008, Thomas established a junior research group at the Karlsruhe Institute of Technology, working on fast electron transfer phenomena in DNA and proteins. He joined Schrodinger in 2013 where he was responsible for the large scale application of free energy calculation methods in pharmaceutical drug design. Since 2017, he heads the Applications Science Department for Europe and supports customers in employing Schrödinger’s Drug Discovery Technology Platform for their research.

Further details from this series can be found at: [ Ссылка ]

This video is an output from the AI3SD Network+ (Artificial Intelligence and Augmented Intelligence for Automated Investigations for Scientific Discovery) which is funded by EPSRC under Grant Number EP/S000356/1

DOI Link: [ Ссылка ]

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