Please click on the name in order to find more information about the Workshop. More Workshops will follow.

Koff-based ligands ranking via BiKiNetics

Unbinding kinetics is emerging as a fundamental observable for the early determination of the clinical efficacy of a candidate drug. In this workshop, we will have the opportunity to setup a protein-ligand unbinding case study using the BiKi Life Sciences software suite. BiKi Life Sciences is the only available software that via our BiKiNetics algorithm is able to accelerate of several order of magnitudes the unbinding process and get quantitative koff-based ligands rankings. This technology is opening new avenues on how we study drug-protein interactions delivering for the first time, in affordable computational times, a koff-based ranking of ligands. All participants upon request will get a 6 months license including all the available BiKi modules including BiKiNetics, MD Binding, Dynamical Pocket Tracking, Clustering, Hydra (Waters scoring).

Visualized Drug Discovery — Decision Support for Any Chemist in Early Drug Hunting

“Will ∆G improve if I put a methyl in ortho?”, “Would an N here improve solubility?”, “Is this a likely torsion?” — Questions like these will be answered in a playful and radically visual way using the most modern graphical tools out there. Using BioSolveIT software we will stimulate the most critical but also most creative assessment there is: Your own brain!

We will use SeeSAR throughout. Starting from a PDB structure, let us test whether we are on solid grounds to further work with this structure. We will modify structures and get instant visual feedback on our ideas with respect to ∆G and ADME. Check for yourself how you resonate with the computer proposal. Go improve ∆G, being guided by the desolvation-aware HYDE Coronas. The recently added Inspirator module is our base for fragment-based work: Replacing a scaffold, leaving the rest in place, or growing to explore a pocket from an exit vector of a fragment binder. Then pursue what is appealing to your eye and to synthetic doability. If time permits, we can navigate chemical spaces of billions to see what might be available in the purchasable chemical neighborhood of our in silico lead idea.

Listening to your top priorities during the course, we will improve your critical perspective on things; let us show you how to succeed in, for example, a structure-based design project. We will stimulate your awareness for the fine balance between desolvation penalties and directed interactions, visually guide you to improve the tightness of fit, make you react to alerts on unusual torsions.

Back home, you will be able to work on your own project. Every workshop participant shall receive a free 8 weeks trial license.

Computer Aided-Drug Design with LigandScout: It’s not just Pharmacophores!

Inte:Ligand supports scientists worldwide with innovative software and workflows for bioactive molecule discovery. Join our workshop to learn modern, user friendly approaches for advanced 3D-pharmacophore modeling, virtual screening, hit triaging, ligand profiling, docking, fragment-based compound design, cavity detection, and how to efficiently make use of information from your molecular dynamics simulations for hit finding. We will use the full LigandScout Suite to explore innovative computer-aided design (CAD) workflows successfully utilized by chemists and modelers in industry and academia to address the major challenges they face in discovering, designing and prioritizing novel bioactive molecules. Advance your molecular design projects these modern workflows.

Orion – a cloud native platform for computer-aided drug design or how can drug-discovery in the cloud work?

Orion is OpenEye’s reimagining of computational drug discovery and design by the cloud. It includes all of OpenEye’s software, extensive tools for data visualization and communication, useful data sources and task-oriented workflows – all in a robust, scalable, cloud environment.

Orion is a ‘cloud native’ platform in that all elements of Orion reside on Amazon Web Services, AWS, the world’s largest on-demand computing facility. Orion uses AWS to deliver easy, scalable, maintenance-free access to hundreds, thousands, or even tens of thousands of processors, unlimited storage and archiving via reliable networks, all backed up by world-class data-security.

Orion is an open platform that allows for straightforward integration of third-party code (customer, academic, vendor). It also includes Floe, a new graphical workflow engine, that makes it simple to construct scripts to take advantage of all that Orion has to offer.

In the workshop we will utilize Orion to combine ligand- and structure-based methods, modify research protocols and analyze the results along the way.

Guided Multi-Parameter Optimisation of 2D and 3D SAR

In this workshop, we will use a combination of 2D and 3D methods to understand and optimize a virtual library of Heat Shock Protein 90 (HSP90) inhibitors. We will explore the library to develop an understanding of the 3D Structure-Activity Relationship (SAR) and then use multi-parameter optimization to further develop the absorption, distribution, metabolism and excretion (ADME) and physicochemical properties of a potent inhibitor without losing efficacy.

The workshop will use our StarDrop™ software and all participants will get a 1-month free trial license to use StarDrop following the workshop. For more information on StarDrop, please visit www.optibrium.com/stardrop or watch some videos of StarDrop in action at www.optibrium.com/community/videos.

Explore targets on the proteome scale!

As there are numerous protein structures in the Protein Data Bank (PDB), we will try to leverage this information in the workshop and study drug targets. We will discover additional proteins which could be of interest and study small molecule ligands. We will inspect the structural similarities in binding sites, predict ligands, inspect binding modes, conglomerate all the data and study it in context of similar protein targets.

The participants will gather additional knowledge on protein drug targets and will be able study their system in the context of all available protein experimental data.

On demand, synthesizable screening libraries are reaching hundreds of millions of compounds, and it is estimated that synthetically tractable enumerated libraries are on the order of up to low billions. To virtually screen such massive libraries using 3D information within drug discovery timelines, the use of GPU-based shape screening methods have demonstrated considerable benefits.

In non-structurally enabled projects, these type of large-scale screenings are often followed by more focused analyses such as pharmacophore modeling. New ideas can be generated via analogue-by-catalogue or synthetically aware de-novo design techniques.

We will discuss these technologies and how they have been incorporated in the latest Schrödinger releases. Furthermore, we will discuss QSAR methods that have historically played a key role in traditional ligand-based workflows – looking forward these are now enhanced by recent developments in deep learning and the possibilities of automated model generation, which have been embedded in our latest AutoQSAR/DeepChem technology.

All these tools can also bring value to structure-based projects, allowing one to go from millions of ideas to a shortlist of compounds that can then be subsequently used in more accurate binding affinity predictions. We will briefly mention some of our internal efforts in this direction.

The workshop is aimed towards participants that are both experienced and new to Schrodinger software, and will give them the chance of first-hand experience with our latest ligand-based design tools.

Achievements

You will have a better understanding of our complete set of LB tools: Phase, Shape GPU, Library enumeration. We will highlight completeness, quality, and speed in the new toolkit. Time and connection permitting, we will include the deployment of models to Medicinal Chemistry via the Live Design platform.