Course info

MOLECULES OF LIFE & MUTATIONS

A practical computer course: molecular modeling and disease explanation

Motto: Never learn a word in isolation.

This course will help you to understand disease in correlation with molecules, their mutations, and specific drugs while performing database searches and molecular modeling on your own. Here, we use only public domain resources you might be able to exploit in your everyday practice.

Prof. Siegfried Schwarz (Medical University Innsbruck, Austria), Assoc. Prof. Jiří Hatina (Faculty of Medicine in Pilsen, Charles University in Prague, Czech Republic) and Dr. Karel Drbal (Faculty of Science, Charles University in Prague, Czech Republic) would like to welcome undergraduate students of Medicine as well as Biology, from the 3rd semester onwards. You are going to learn molecular modeling methods, perform your individual homework and give a final 10-minutes presentation in English within this 3-day interactive and interdisciplinary course.

This course gives you a general overview of our understanding of the normal as well as abnormal protein structures originating from particular gene mutations and/or allosteric effector function in health as well as in a diseased state. The introduction provides a couple of examples of structure-function relationships in human medicine.

A practical computer course: 
molecular modeling and disease explanation

Motto: Never learn a word in isolation.

1st day / Lectures

• Siegfried Schwarz: Physiology cases 

  AVP and diabetes insipidus (practical)

• Karel Drbal: Immunology cases

  Innate immunity structures and diseases

2nd day / Lectures & Practical (RasMol)

• Jiri Hatina:

  Stem cell cases & Sox2

• Siegfried Schwarz
  

  Sox2 structure and mutations leading to microphthalmia (practical)

3rd day / Other tools

• Siegfried Schwarz

  SARS-CoV-2 structure of S protein and epitopes of neutralizing antibodies (practical)

• Karel Drbal:

  Mol*

• Daniel Rozbesky:

  PyMol

• Vaclav Veverka:

  Chimera and Cryo-EM data

• Molecule/disease assignment for the presentation

The course will help you to understand disease in correlation with molecules, their mutations, and specific drugs while performing database searches and molecular modeling on your own. Here, we use only public domain resources you might be able to exploit in your everyday practice as the basis for evidence-based medicine in the future. We will show pathophysiological states in the endocrine, nervous, and immune systems. The course will help you to understand a health/disease correlation with the use of molecules, their mutations, and interactions with specific drugs. 

See a recent commentary: PubMed / pdf. Some more colleagues will participate this year - mainly researchers in the field of structural biology: Prof. Siegfried Schwarz (Medical University Innsbruck, Austria), Assoc. Prof. Jiří Hatina (Faculty of Medicine in Pilsen, Charles University, Czech Republic), Dr. Karel Drbal, Dr. Marian Novotný, Dr. Daniel Rozbeský and Dr. Václav Veverka (Faculty of Science, Charles University, Czech Republic).

We would like to welcome undergraduate students of Medicine as well as Biology, from the 3rd semester onwards. You are going to learn molecular modeling methods, perform your individual homework and give a final 10-minutes presentation in English within this 4-day interactive interdisciplinary course. 

This course provides a general overview of our understanding of the normal as well as abnormal protein structures originating from a particular gene mutation and/or allosteric effector function in health as well as in a diseased state. The introduction provides a couple of examples of structure-function relationships in various fields of medicine. In the second part, we follow with a hands-on course in a computer room where attendees receive a detailed step-by-step description of how to perform practical molecular modeling on PC using appropriate open-source software (RasMol) and alternative SW (PyMol, LiteMol).

Having the X/Y/Z coordinates of atoms, as deposited in the Brookhaven Protein Data Bank (PDB), students can visualize and manipulate 3D structures of crystallized proteins, alone or after interaction with small or large ligands such as their substrates, drugs, DNA, or other proteins. Attendees will learn also how to use the OMIM (Online Inheritance in Men) Data Bank from where they can retrieve the published mutations and corresponding disease pathology. Thereby, various structural characteristics can be recognized: domains of certain structure or charge, hydrophobicity or shape, and other properties, which can serve e.g. as a ligand-binding domain, a DNA-binding domain, a drug-metabolizing pocket, or as a domain for any other biological function. The real power of molecular modeling resides in its informative value displaying the molecular structure, in total or in portions thereof, in different formats such as wireframe, protein backbone, atoms, overall surface, etc. It is possible to turn the molecule in all directions and to see in real-time various aspects of its structure. Most importantly, points of mutation, as documented in the OMIM and other databases, can be mapped into a structural model in order to understand which function of the protein would thus be altered and whether this change in structure would result in loss-of-function or gain-of-function showing recessive or dominant effect. The link between arginine vasopressin precursor (AVP) and Diabetes insipidus, as well as various clinical phenotypes associated with the mutant androgen receptor, serve as illustrative and informative examples.

At the end of the lectures, students will get assigned an individual mutated protein and a corresponding disease pathology that they have to elaborate on as homework according to the demo example they have seen in the course. Each student should prepare a short (10 minutes) lecture in PowerPoint or alternative and discuss her/his observations, published data, and clinical outcomes. 

On the last day of the course (after 2-3 weeks), students are going to present their homework in front of all attending colleagues including teachers. As such, everyone can learn from the others - kind of a multiplication effect. We will meet for the presentations in the lecture room or online if you cannot participate in person. 

The course is based on a textbook published by Siegfried Schwarz: MOLECULES OF LIFE & MUTATIONS (Karger, Basel 2002, ISBN: 978-3-8055-7395-5), in which structures of 150 most important molecules are displayed.
https://www.karger.com/Book/Home/227359

Look at the Membrane receptors chapter.