2022-12-14 Molecular Modeling with Schrödinger-Suite (hmms1w22)

This course co-organised by LRZ and Schrödinger, Inc. combines lectures about protein preparation, docking and designing ligands using the Schrödinger Suite, basics of computational modeling and PyMOL on the first day with lectures about advanced structure preparation and introduction to free energy methods on the second day. 

Preliminary Agenda

Content

Day 1: A Beginners’ Guide to Maestro, Preparation, Docking and Designing Ligands in a UX Friendly Interface

This session designed for beginners to the Schrödinger software focuses on learning to navigate the Maestro interface and how to perform docking of small molecules.

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.

All material will be provided during the course, however, you may wish to prepare prior, using the following resources:

Ligand Designer (features, highlights, demo videos)

• https://www.schrodinger.com/science-articles/ligand-designer

Maestro, Preparation and Docking…

• https://www.schrodinger.com/training/maestro11/home
• https://www.schrodinger.com/learn/training/smdd

PyMOL@LRZ 

PyMOL, developed by Warren L. DeLano as of 1998, has become the most popular tool for preparing publication-ready renderings of three-dimensional biomolecular structures. This session provides hands-on introduction on how to visualize molecular structures in PyMOL, aiming at the generation of state-of-the-art ray-traced images. We will learn to operate PyMOL both by using the graphical user interface and from the command line. The tutorial is set up for researchers working in the biomedical field and individuals with a general interest in effectively applying PyMOL. 

Day 2: A Deep Dive into Structure Preparation and Preliminary Analysis, and Understanding the Thermodynamics of Protein-Ligand Binding.

This session covers the intricacies of preparing protein systems for computational work, as well as 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 session 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 will be provided during the course, however, you may wish to prepare prior, using the following resources:

WaterMap (Webinars and Tutorials):

• Schrödinger Training Center

Prerequisites

For the PyMOL session:
Basic Python and Linux shell (bash) knowledge.
Your own laptop/system is needed for the hands-on sessions, you need the packages "anaconda python" and "pymol" (use conda install -c conda-forge pymol-open-source), more details will be sent before the course. 

For the other sessions:
None

Hands-On

Participants will have the opportunity to gain hands-on experience on basic workflows which include how to build systems appropriate for MD, running MD and basic and advanced trajectory analysis tools. Participants are expected to use their own system/laptop. Further information on the Schrödinger software suite at LRZ can be found under https://doku.lrz.de/display/PUBLIC/SCHRODINGER

Language

English

Lecturers

Schrödinger software experts and LRZ Biolab team.   

Prices and Eligibility

The course is open and free of charge for people from academia and industry from the Member States (MS) of the European Union (EU) and Associated Countries to the Horizon 2020 programme.

Registration

Please register with your official e-mail address to prove your affiliation.  Please note: This course is offered in cooperation with Schrödinger, Inc. Some of your personal data will be transferred to Schrödinger (title, first name, surname, institution, country, email, course). The legal basis is in accordance with Article 6(1)(b) GDPR. Please see also our data protection notice (in German: https://www.lrz.de/datenschutzerklaerung/).

Withdrawal Policy

See Withdrawal

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