CBI 学会 2022 年⼤会（2 ⽇⽬）スポンサードセッション
⽇時︓10 ⽉ 26 ⽇（⽔）15:30-17:00

Structure-Based Lead Optimization in Orion®
– Progressively Improving Estimates of Binding Affinity –OpenEye, Cadence Molecular Sciences

Lead optimization happens in cycles, beginning with the core of the lead andgenerating a great many candidate analogs based on R-group substitution. In theend, only a few of these candidates will be synthesized to be assayed. Using
computational methods to reduce the great many candidates to the few involves
progressive stages of refinement aimed at rejecting a majority of worse candidates
from the previous stage. As the stages progress, the set of remaining candidates
becomes smaller and of higher quality, requiring a gradually improving estimate ofbinding affinity. We will look at this process in the context of the protein structurebased approach. All steps in this process will be performed seamlessly in Orion
while taking advantage of massive parallelism in the Cloud. We will present thesequential stages of a cycle of lead optimization, beginning with generativemodeling and progressing through to relative binding free energies. More detail willbe given on the use of the relatively new Non-Equilibrium Switching (NES) method
for relative binding free energies.

お問い合わせ先︓oe_japan@eyesopen.com
https://www.eyesopen.inc /orion®

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Trusted OpenEye ScienceOrion® delivers the OpenEye computational tools scientists havetrusted for more than twenty years in an integrated web platformbacked by the computer power of Amazon Web Services.
• Run ligand-based or structure-based virtual screenings,
molecular dynamics (MD) simulations, free energy predictions,quantum mechanics calculations, sequence analysis, and morefrom just a web browser• Perform ultra-fast 2D and 3D search of over 4 billion stereo-enumerated
commercially available molecules and 40 billion conformers• Integrate third-party or in-house tools• Collaborate with colleagues without file transfers and formatting

Orion Platform

The Orion platform provides all the tools and data needed to allow
calculation, analysis, collaboration, and decision-making in one
environment.

The Orion Platform Provides:• An integrated web-based environment to design, calculate,view, and analyze all your computation and modeling projects,
in real-time• Freedom to program your own calculations that use diverse
hardware• Connectivity to Orion’s flexible storage system, including
large-scale distributed I/O• Automatic parallelization to optimize your workflows• A single platform for your data and applications, eliminating theneed for data transfer and app switching and letting you collaborate with your team in real-timeOrion Science Suites
OpenEye is renowned for its chemical modeling applications and toolkits. All of its science has been through rigorous validations andpeer-reviews. Running these trusted solutions on AWS means you can now solve modeling questions that were previously impossible due tocompute-time or hardware limitations.

Small Molecule Discovery Suite
Structure- and Ligand-based Design
The Small Molecule Discovery Suite in Orion® provides a complete range of easy-to-use ligand- and structure-based modeling workflows for
all your therapeutic project needs, such as increasing the hit rate of your virtual screen, optimizing affinity of lead candidates, and predicting
off-target effects. Learn more at: https://www.eyesopen.com/orion/small-molecule-discovery-suite

For more information on Orion and additional science suites,
please visit our website at www.openeye.inc/orion
or contact us at oe_japan@eyesopen.com

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