The 2nd virtual edition of the NovAliX Conference “Biophysics in Drug Discovery” took place last March 9-12. This event brought together 235 participants (85% from industry) from 18 different countries from all continents, representing 129 companies and institutions.

The conference started with a brief introduction from conference chairman Jean-Paul Renaud. Chaohong Sun from Abbvie chaired the first session, dedicated to COVID-19, where Xue Wang from Thermo Fisher Scientific showed structural and functional results on a SARS-CoV2 spike variant, illustrating the power of cryo-EM, followed by Alexander Metz from Idorsia who presented a structure-based approach to identify SARS-coV-2 3CL protease inhibitors.

A very exciting Session 2 dedicated to proximity-induced drug discovery started with a lecture from Dirksen Bussiere from Eli Lilly on the mechanism of action of the anticancer agent indisulam in the targeted protein degradation of RBM39. Dzung Nguyen from Philipps-Universität Marburg presented the targeting of a cryptic binding pocket induced by the disruption of a homodimeric protein–protein interface. Closing the day, Michelle Arkin from University of California delivered the first keynote lecture on the dissection of protein–protein interaction networks.

MariJean Eggen from Eli Lilly chaired Session 3 on Wednesday 10th dedicated to integrative structural biology & biophysics. Patrick Griffin from The Scripps Research Institute talked about the fine tuning of the nuclear receptor RORg signaling. Three oral communications completed the session with several topics spanning the combined use of ligand-based NMR and crystallography (Ariele Viacava Follis from EMD Serono), fragment screening (Troy Johnson from University of Texas MD Anderson Cancer Center) and a fragment- and structure-based approach to identify cysteine desulfurase inhibitors (Ami Boncella from the Colorado School of Mines). Finally, Daniel Wyss from Merck presented the characterization and conformational assessment of STING modulators.

Session 4, a whole day sponsored by Thermo Fisher Scientific, focused on cryo-EM for drug discovery. Jeffrey Lengyel from Thermo Fisher Scientific chaired the day. Corey Strickland from Merck gave the first lecture, with a great overview on how Merck implemented its cryo-EM platform and how it helped Merck to support its drug discovery programs. Lionel Rougé from Genentech illustrated the use of cryo-EM in drug discovery with an example of structural characterization of TRPA1 inhibitors. Kenneth Borrelli from Schrödinger showed how to improve the modeling of protein-ligand complexes into cryo-EM data. Finally, Patrick Sexton from Monash University presented the use of GPCR cryo-EM structures in drug discovery. The day ended with a panel discussion about the use of cryo-EM to advance drug discovery for difficult targets where Benjamin Apker from MiteGen, Denis Zeyer from NovAliX and Corey Strickland from Merck exchanged different ideas and insights.

Session 5 on the last day was dedicated to advances in biophysical techniques. Reto Horst from Pfizer gave a wonderful talk on the NMR study of the ligand-dependent structural plasticity of TrkA kinase. Two oral communications followed, the first one by Terence Strick from Ecole Normale Supérieure on the use of a DNA-based nanoscale actuator for the single-molecule detection of drug-protein interactions, and the other one by Alessandra Feoli from the University of Salerno on the development of a microscale thermophoresis-based method to screen inhibitors of the methyl-lysine reader protein MRG15. William Pomerantz from University of Minnesota presented the use of protein-observed 19F NMR as a ligand discovery tool. Volker Gatterdam from Lino Biotech AG then presented focal molography, a new nanotechnology-based bioanalytical tool to characterize membrane proteins within living cells. Yuliya Dubianok from University of Oxford presented the use of crystallographic soaking as a tool for fragment hit prioritization. Last but not least, Bret Nannenga from Arizona State University shared delivered the second keynote lecture on the methodology and applications of microcrystal electron diffraction (Micro-ED).

We had a wonderful time and would like to thank all participants for their numerous interesting questions and comments. We would also like to thank all exhibitors for their support and presentations. And we are most grateful to our Platinum Sponsor Thermo Fisher Scientific for setting up the very exciting full-day session on cryo-EM.

The next NovAliX Conference “Biophysics in Drug Discovery” will be an Asian edition, again virtual. We will wait until March 2022 to go back to a live event – hopefully in Munich.See you at the next NovAliX Conference !

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