Schrödinger Maestro Suite hands-on workshop
The first day of the workshop covers an introduction to Maestro and is aimed for new users or beginners on small molecule modelling tools. The second day focuses on more advanced topics. It's possible to participate on-site at Espoo or join via zoom (link provided for registered participants). Registration is required, but the event is free of charge both on-site and on-line.
DAY 1 Wednesday 7th December 2022
Title: A Schrödinger Workshop: A beginners’ guide to Maestro, Preparation, Docking and Designing Ligands in a UX Friendly Interface
Tools: Maestro, Ligprep, Protein Preparation Wizard, SiteMap, WaterMap, Glide and Ligand Designer
Level: Beginners
Abstract (day 1):
If you are interested in learning to navigate the Maestro interface and how to perform docking of small molecules, then we will focus on these topics in a 4 hour hands-on workshop designed for beginners to the Schrödinger software.
The main Maestro interface houses all the tools that are required to bring in your starting small molecules and protein system, so that they may be prepared correctly. Once you are comfortable with the fundamentals of preparing your raw materials, we will move on to understanding more about the binding site and its features which will help us think about how a ligand might interact with it. This forms a fundamental basis for understanding our docking results, so we will start by setting up and running docking jobs, and analysing how the resulting docked compounds fulfill the basic criteria of shape and molecular interactions that lead to the final Glide Scoring term. Finally, we will explore ligand design in a more automated fashion using the Ligand Designer GUI which facilitates on-the-fly ideation through ‘build and dock’ workflows. Through the use of embedded libraries of building-blocks, users can modify their initial idea in many intuitive ways: from attachment points on the bound ligand; the free and viable space in the binding site; through to picking specific residues in the protein or specific waters in the binding cavity to guide the design process.
Preparation
All material for the workshop will be provided on the day, however, you may wish to prepare prior, using the following resources. Note, if you participate remotely, you need to install Maestro. If you're affiliated to a university in Finland, see instructions at the CSC Maestro page. Also, if you want to run jobs on Puhti, please set up a user account at CSC in advance!
- Ligand Designer (features, highlights, demo videos)
- Maestro, Preparation and Docking
- Small molecule docking
- Maestro, CSC help page
DAY 2 Thursday 8th December 2022
Title: A Schrödinger Workshop: A deep dive into structure preparation and preliminary analysis, and understanding the thermodynamics of Protein-Ligand binding.
Tools: Maestro, Advanced Protein Preparation, WaterMap
Level: Mid to Advanced
Abstract (day 2):
If you’re interested in diving deeply into more advanced topics in computational drug discovery, in this second 4-hour workshop we will cover the intricacies of preparing protein systems for computational work, as well as discuss in-depth the thermodynamics of protein-ligand binding and its implications for the computational drug discovery process.
While the protein preparation workflow introduced in the previous day’s workshop automates many of the steps necessary to go from a crystal structure model of a protein to a system ready for computational simulations, there are many quality and validation checks that can give you additional confidence that your structural data is well-suited for your purpose. We’ll go through the main function-, sequence-, X-Ray- and preparation-related checks, collecting them in a handy protein preparation checklist.
We’ll then move on to an interactive discussion about how a good description of the thermodynamics of protein-ligand binding can guide researchers during the drug discovery process. Stark differences in the potency of similar ligands can be caused by subtle changes in the hydration of the binding pocket, and we’ll guide you through using WaterMap to understand, quantify and use these effects to your advantage. Additionally, we’ll discuss why docking scores are insufficient to rank-order compounds during the lead-optimization phase of drug discovery, and discuss computational approaches to approximating binding affinities.
Preparation
All material for the workshop will be provided on the day, however, you may wish to prepare prior, using the following resources. Note, if you want to run parallelized jobs on CSC resources, you'll need a CSC account, and membership on a project that has access to Puhti before the workshop. Please, consult CSC Docs on how.
WaterMap (Webinars and Tutorials): Schrödinger Training Center
Agenda and Times (EET, GMT+2)
Day 1 Wednesday 7th December, 2022
09.30 Set up time (login checks)
09.45 Welcome (Coffee and Introduction) from Account Manager, Rita Podžuna
10.00 Maestro, Preparation of Proteins and Ligands, Studying the Binding Site
12.00 Lunch
13.10 Docking with Glide and Designing with Ligand Designer
15.10 Additional QA, Close
Day2 Thursday 8th December, 2022
09.30 Set up time (login checks)
09.45 Welcome (Coffee and Introduction) from Account Manager, Rita Podžuna
10.00 Advanced aspects of protein preparation
12.00 Lunch
13.10 Thermodynamics of protein-ligand binding: WaterMap; estimating binding free energies
15.10 Additional QA, Close
Lecturers from Schrödinger Inc.:
- Dr. Rita Podzuna (Executive Director)
- Dr. Mila Krämer (Senior Scientist)
- Dr. Jas Bhachoo (Principal Scientist)
Registration DLs
On-site registration by 1st December at the latest (on-line continues).
We aim for a hybrid event: on-site at CSC and on zoom. The on-site part will be organized only if at least 10 people register for on-site. The cutoff date is Thursday 1st December. If you want to come on-site register before that! On-line registration will continue after that.