Hi all, Our next online industry talk will be given by Huafeng Xu of Atommap (see title and abstract below) on Wednesday 26 July 2023 at 3:30 pm UK time. Registration is free, but required to get the Zoom link. Details and link to registration can be found at www.ccpbiosim.ac.uk/atommap2023<http://www.ccpbiosim.ac.uk/atommap2023>.
Best wishes, Sarah Title: Computation-driven drug discovery Abstract: We are witnessing a rapid rise of computation in the drug discovery industry. The renewed excitement about computational modeling is attributable to the dramatic growth of computing power and substantial and continuous improvements in the models of computational chemistry and biology, including both progress in mature physics-based models and the emergence of deep neural network (DNN) and other machine learning models. Here, I illustrate the use of multi-scale, multi-fidelity molecular modeling in computation-driven drug discovery, focusing on exploiting the conformational dynamics in biomolecules to enable new therapeutic opportunities. By incorporating biophysical data, such as hydrogen-deuterium exchange (HDX) and nuclear magnetic resonance (NMR), into molecular dynamics simulations (augmented by enhanced sampling techniques), we turn the low-resolution experimental measurements into accurate models of structural ensembles of proteins at atomistic resolution, yielding novel structural hypotheses for drug design. Using this approach, we have optimized a small molecule agonist for both affinity and stabilization of the active conformation of Stimulator of Interferon Genes (STING) and rapidly advanced the program into clinical trial, and we have designed an active targeted protein degrader of SMARCA2 based on a modeled conformation of the SMARCA2-degrader-VHL ternary complex previously unobserved but subsequently confirmed in crystallography. I discuss the path to general application of computation-driven drug discovery. ######################################################################## To unsubscribe from the CCP4BB list, click the following link: https://www.jiscmail.ac.uk/cgi-bin/WA-JISC.exe?SUBED1=CCP4BB&A=1 This message was issued to members of www.jiscmail.ac.uk/CCP4BB, a mailing list hosted by www.jiscmail.ac.uk, terms & conditions are available at https://www.jiscmail.ac.uk/policyandsecurity/
