of the crowdsourced simulations
We must find effective treatments of COVID-19 and potentially to other coronaviruses.
To achieve this goal we NEED YOUR SUPPORT, YOUR TALENT and YOUR SIMULATIONS!
We want to collect the BEST POSSIBLE CHEMICAL LIBRARY of NOVEL INHIBITORS OF SARS-COV-2 targeting the most relevant viral proteins combining as much as possible
VIRTUAL SCREENING SIMULATIONS and AI PREDICTIONS generated by THE BEST DRUG HUNTERS WORLDWIDE.
If you are a MEDICINAL COMPUTATIONAL CHEMIST or a AI/ML EXPERT and you want to support the global fight against SARS-COV-2,
HELP US to select the most promising molecules against the SARS-COV-2 targets.
We will use the knowledge you all generate to ASSEMBLE, ACQUIRE and EXPERIMENTALLY VALIDATE
the first CROWDSOURCED ANTI SARS-COV-2 CHEMICAL LIBRARY.
The MEDIATE initiative as part of the EXSCALATE4COV project will provide you selected chemical spaces to be evaluate: a DeNovo synthesizable chemical space, commercially
available compounds, natural products, oligo-peptides, safe in man drugs in combination with Ready-to-virtual-screen 3D structures
and microseconds molecular dynamics simulations of all SARS-COV-2 biological targets with allosteric and orthosteric binding site mapped.
Use MEDIATE chemical libraries and 3D models to perform YOUR ACTIVITY PREDICTIONS and SUBMIT YOU RESULTS on our web portal, we want to collect an EXTENSIVE IN SILICO POLY-PHARMACOLOGICAL PROFILE of the reference chemical space and then with the support of state of the art MACHINE LEARNING TECHNIQUESgenerate a GLOBAL MODEL to select the most promising molecules.
To support your valuable effort EXSCALATE4COV project offers you 10,000,000* hours of calculations on the CINECA super computer infrastructure
and the possibility to publish your results on a special issue of the International Journal of Molecular Sciences (ISSN 1422-0067) (www.mdpi.com ) dedicated to the project.
*[up to 200K CPU hours for any single request]
of the crowdsourced simulations
Generation of a single Final Ranking by using
ML and AI technologies thanks to the SAS platform
Purchase of the best candidates
selected in phase 2
’The libraries will be tested
in all our COVID19 assay and the in all our EXSCALATE4COV assay and
the most promising could be crystallized
Results on the compounds will be published
in public portals and make available
MEDIATE project put at your disposal the VIRAL PROTEINS with the higher pharmaceutical interest and the BINDING SITES identified with our method recently published in the International Journal of Molecular Sciences. (for more details www.mdpi.com )
This novel strategy for pocket mapping, based on the combination of pocket and docking searches is proved successful in precisely characterizing a set of SARS-CoV-2 druggable binding pockets including both orthosteric and allosteric sites, which will be very useful for your MEDIATE virtual screening campaign.
All compounds were converted to 3D and prepared with Schrödinger’s LigPrep tool (Schrödinger Release 2020-2: LigPrep, Schrödinger, LLC, New York, NY, 2020.). This process generated multiple states for stereoisomers, tautomers, ring conformations (1 stable ring conformer by default) and protonation states. The Schrödinger package Epik was used to assign tautomers and protonation states that would be dominant at a selected pH range (pH=7±1).
Ambiguous chiral centers were enumerated, allowing a maximum of 32 isomers to be produced from each input structure. Then, an energy minimization was performed with the OPLS3 force field ([Harder2016]). Duplicates among the libraries were removed.