New modalities for 3D virtual screening of ultra-large chemical spaces

Date

Date: Tuesday 5th March 2024
Time: 2pm GMT / 4pm CET / 10am EDT / 7am PST
Duration: 45 minutes
Format: Webinar

Abstract

Join us for this webinar hosted with Mark Mackey, Chief Scientific Officer, Cresset and Dmytro Radchenko, Head of Parallel Chemistry, Enamine.

3D virtual screening has traditionally been performed by generating conformations of the molecules to be screened and then performing some sort of computation on each conformation, either as separate processed (ligand similarity methods) or simultaneously (docking). However, this approach becomes computationally infeasible if it is desired to screen ultra-large chemical spaces, as the computational cost and storage cost quickly become astronomical as the size of the space increases. As a result, virtual screening on ultra-large chemical spaces is currently mostly performed using 1D methods such as fingerprints. We present an alternative approach, Ignite™, utilizing a knowledge of the construction of the virtual space in terms of synthons and reactions, that allows the rapid screenout of large parts of the space. Efficiency gains of more than a hundredfold can be achieved, allowing the 3D virtual screening of ultra-large spaces with relatively modest CPU resources. We provide examples of this technology being applied to Enamine REAL Space, demonstrating a strategy for fast screening of billions of compounds that can be synthesized with over 80% success rate and delivered for wet screening in a month’s time.

About the presenters

Mark Mackey

Mark graduated from the University of Tasmania in 1992 with a BSc in Chemistry, Physics and Mathematics. Between 1988 and 1992 Mark was awarded the following  accolades: Chemistry Honors Prize at University of Tasmania; Dean’s citation for outstanding undergraduate and Honors achievements; University Medal from University of Tasmania; ICI Australia Ltd Prize for third year chemistry; Masson Memorial Prize for top chemistry graduate in Australia.

In 1993 Mark moved to the University of Cambridge where he was awarded his PhD in 1997. It was during his time at Cambridge that Mark first worked with Dr Andy Vinter, founder of Cresset.

Upon completion of his PhD Mark worked as a Molecular Modeler and Senior Research Scientist for Napp Pharmaceuticals and Merck Sharp & Dohme respectively.

In 2002 Dr Vinter invited Mark to join him as a founder member of Cresset. Mark has designed and added fundamental science to tools that are now accepted and used by many pharmaceutical, agrochemical and academic institutions across the world. In 2010 Mark was appointed as CSO of Cresset.

Mark is a Fellow of the Royal Society of Chemistry and on the Board of the Open Force Field Consortium.

Dmytro Radchenko

Dmytro S. Radchenko, born in Zaporizhzhia in 1985, is an organic chemist with both an academic and industry background. In 2002, he won a silver medal at  the 34th International Chemistry Olympiad for high school students. He then went on to graduate with honors from the Chemical Department of Taras Shevchenko National University of Kyiv in 2007. After graduation, Dmytro began working as a Junior Researcher at the same university while simultaneously working at Enamine LTD.

In 2011, Dmytro obtained his PhD degree (Candidate of Sciences Degree) in Organic Chemistry at Kyiv National Taras Shevchenko University under the supervision of Prof. Igor V. Komarov. In 2014-2015, he joined Anne Ulrich’s group as a postdoctoral fellow at the Karlsruhe Institute of Technology in Germany, where he was awarded the Alexander von Humboldt Fellowship.

Dmytro has worked for Enamine since 2007, with the exception of his post-doctoral leave in 2014-2015. He began his industry career as an organic chemist and later became a Team Leader before transitioning to the position of Production Manager at the Building Blocks synthesis department. After returning to Enamine in 2015, he worked at the Parallel Chemistry department and became the Head of Parallel Chemistry in 2018. In this role, he has various responsibilities and interests, including the enlargement of the Enamine REAL space/database, synthesis of large screening libraries using parallel chemistry, supervision of pre-plated libraries of screening compounds, and development of in-house tools to work with chemical data.

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