Schrödinger Maestro Workshop

Welcome to Schrödinger Maestro workshop at CSC! This year’s workshop focuses on small molecule drug discovery and drug formulation with Schrödinger Maestro software suite. No prior simulation experience is required. The focus will be on hands-on experience and application.

It’s possible to participate on-site at CSC premises in Espoo, or join via Zoom (link provided for registered participants). Registration is required, but the event is free of charge both onsite and online.

Day 1: Wednesday, December 4th 2024

Small molecule drug discovery part I: Computational modeling can support and enhance various stages of the drug discovery and design process. The Maestro interface contains all the tools needed to import and prepare your starting small molecule and protein system, and provides access to the computational tools within the Schrödinger suite for life sciences. In this session we will go through the necessary steps to prepare ligand and protein structures. We will then explore ligand design in an automated fashion using the Ligand Designer GUI, which facilitates on-the-fly ideation through ‘build and dock’ workflows. Finally, we will set up and run docking calculations with Glide, and analyze how the resulting docked compounds satisfy the basic criteria of shape and molecular interactions that lead to the final Glide scoring term.

Drug formulation part I: A smart, strategic drug formulation can efficiently advance your drug development projects and inform downstream processes. Simulations can help selecting and combining the right formulation ingredients in the appropriate manner. In this session, we will introduce our Materials Science Suite for materials science applications, demonstrating the tools available for pharmaceutical formulations and drug development processes. We will guide you through building systems, running molecular dynamics simulations, and calculating the miscibility of active pharmaceutical ingredients (APIs).

Day 2: Thursday, December 5th 2024

Drug formulation part II: In this session we will focus on extracting key properties and information from simulations of various formulations. Prediction of chemical and physical stability of formulations in storage conditions are pivotal for understanding a product’s shelf life. In particular, prediction of the glass transition temperature (Tg) for APIs and mixtures is an important indicator of thermodynamic stability in the solid state and a relevant information for the
manufacturing process. Similarly, predicting the tendency for a formulation to uptake water at certain humidity conditions is important for knowing its behaviour and stability in different storage conditions. Using MS Maestro and the tools available in the MS Suite, we will calculate Tg and hygroscopicity of APIs and API/polymer mixtures. Finally, we will introduce Coarse Grained simulations, useful for describing those complex and evolving structures, often in fluid states, that play a crucial role for API delivery.

Small molecule drug discovery part II: By studying the dynamics of a molecular system in a thermodynamic environment, we can investigate processes such as protein folding, protein-protein or protein-ligand interactions, and gain new structural insights for drug discovery and design. In this session we will learn how to set up, run and analyze the results of an unrestrained all-atom molecular dynamics simulation using Desmond and Maestro. We will focus on a protein-ligand complex and go through different ways and tools to analyze a simulation. The analysis will improve our understanding of the binding pocket and the interactions between protein and ligand.

Preparation

All material for the workshop will be provided on the day. It is recommended that beginners watch the “Getting going with Maestro/MS Maestro” video series to familiarize themselves with the interfaces of the Schrödinger suite for life science and material science, respectively. In addition, it may be helpful to watch this video on YouTube to get an introduction to the basic concepts of molecular dynamics, as they will be covered only briefly in the workshop.

Also note that CSC has a limited number of free-of-charge seats for introductory-level Schrödinger Online Certification courses available upon application. Apply for a course coupon here.

Note, if you participate remotely, you need to install Maestro locally yourself. The same applies if you intend to use your own laptop on-site instead of provided workstations. If you’re an academic user affiliated with a Finnish higher-education institute, see our Maestro page in Docs CSC for installation instructions, as well as general details on using Maestro in CSC’s computing environment.

Also, if you want to run parallelized jobs using CSC resources, you’ll need a CSC account and membership in a project that has access to Puhti before the workshop. Please consult Docs CSC on how to create an account and join a project.

Agenda and Times

Day 1: Wed, Dec 4 2024

09:30 Set up time
09:45 Welcome
10:00 Intro to Maestro, protein preparation and studying the binding site
12:00 Lunch
13:00 Designing ligands with the Ligand Designer and docking with Glide
15:00 Introduction to Schrodinger Materials Science
15:30 Intro to MS Maestro
16:00 Building all atom systems and running simple MD workflows
17:00 Additional Q&A, closing

Day 2: Thu, Dec 5 2024

09:30 Setup & welcome
09:45 Running Desmond on CSC Supercomputers
10:15 Solid formulations properties
12:00 Lunch
13:00 Structured liquids and introduction to CG simulations
14:00 Going to larger systems: MD simulation of a protein-ligand complex
15:30 Additional Q&A, Closing