2021-12-06 Molecular Modeling with Schrödinger-Suite (hmms1w21)

Molecular Modeling with Schrödinger-Suite

This wokshop co-organised by LRZ and Schrödinger, Inc. combines lectures about Drug Discovery (Biologics modelling, Molecular Dynamics Simulations) using the Schrödinger drug discovery platform on the first day with lectures about Materials Science (Polymer innovation, Surface Modeling) using the the Schrödinger Materials Science Suite on the second day. These topics can be selected individually during registration.

Preliminary Agenda

Content

Day 1: Drug Discovery

Drug Discovery (Protein-protein docking, mAB modeling, protein design/mutagenesis ; Molecular dynamics & metadynamics simulations)

The Schrödinger drug discovery platform encompasses solutions for predictive physics-based modeling, machine learning, data analytics, and collaboration. Through hands-on exercises and interactive presentations, we will work together with the attendees on industrial-level computational modelling tasks in the fields of chemical & biological molecular design. Beginning from target analysis and preparation of compound library via enumeration and virtual screening cascades involving ligand- and structure-based methodologies. 

09:00-10:30 Part I: Biologics modelling 

• Antibody Homology Modeling
• Protein-Protein Docking
• Protein Design/Mutagenesis

Antibodies have emerged in recent years as one of the major classes in protein-based therapeutic biologics. Despite successes in development through experiments, continued exploitation of antibodies relies on more efficient ways to design and optimize these molecules. Computational in silico technologies hold promise in advancing the field by providing faster and cheaper results. 

In this part of the workshop, participants will learn how reliable computational solutions can be applied during research and development to direct experimental efforts, with the aim of reducing costs and timelines. 

Participants will have the opportunity to gain hands-on experience on typical rational design techniques such as antibody homology modeling, optimization and antibody-antigen interface prediction.

10:40-12:00 Part II: Molecular Dynamics Simulations 

• MD Simulations of GPCRs
• Analysis of MD Trajectories
• Metadynamics Simulations

G Protein-coupled receptors (GPCRs) are membrane proteins that play a major role in modern therapeutics. This becomes apparent when considering the large number of FDA-approved drugs (one-third of small-molecules) and high percentage of drug candidates interacting directly with GPCRs. The increasing number of high quality receptor structures, further accelerated  by advances in cryoEM, holds the promise to expand computational in silico technologies to GPCRs so far considered inaccessible for structure-based design.

In this part of the workshop, participants will learn to run molecular dynamics (MD) simulations of membrane proteins effectively using best practices. 

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. If time allows, the  workshop will offer a basic introduction to metadynamics simulations.

13:00 - 15:00 PyMOL

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 workshop 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: Materials Science 

10:00-11:30  Part I: Polymer innovation with the Schrödinger Materials Science Suite 

Polymeric materials have found widespread applications across a diverse range of industries. Typically, the performance of polymers depends on a multitude of parameters which makes traditional research approaches, relying on experiments solely, slow, inefficient, and prohibitively expensive. Molecular modelling approaches can significantly speed up the process of polymer discovery and characterization by filtering out unsuitable materials at an early stage and therefore reducing the number of experiments significantly.

In this part of the workshop we will demonstrate how the Schrödinger Materials Science suite can be used to accelerate polymer innovation; in particular, we will discuss:

• Automated builders to create realistic structural models

• Sophisticated molecular dynamics workflows to obtain equilibrated polymer structures, analyze key properties, and investigate environmental effects, like moisture, on the polymer structure

• Intuitive analysis tools to visualize and interpret the results

11:40 - 13:00 Part II: Surface Modeling with the Schrödinger Materials Science Suite 

Computing atomic-scale models of surfaces and interfaces with density functional theory (DFT) is a powerful way to address research questions in heterogeneous catalysis, thin film deposition (CVD, ALD etc), sensors, photovoltaics and batteries.  This hands-on tutorial introduces the basic steps that are needed to set up such a surface model and compute the atomic and electronic structure with Quantum ESPRESSO.  Rutile TiO2 is used as the sample substrate, and building a slab model is demonstrated for the bare (1 1 0) and (1 0 1) surfaces.  DFT results are used to calculate the surface energy and thus assess convergence of the models.  Adsorption onto the surface is then investigated using trimethylphosphine as the sample gas molecule, checking a variety of adsorption modes, and using DFT to compute the adsorption free energy as a function of temperature and pressure.  This reveals how surface reactivity changes with experimental conditions.

Prerequisites

For the PyMOL session:
Basic Python and Linux shell (bash) knowledge.
If you want to use your own laptop for the hands-on sessions, you need the packages "anaconda python" and "pymol" (use conda install -c conda-forge pymol-open-source)

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. The exercises can be done on your own system/laptop and the CoolMUC-2 Linux cluster at LRZ. 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

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