Teaching

Molecular BioMedicine 

is a broad field where physical, chemical, biological and medical techniques are used to identify the underlying causes and mechanisms of disease at the genetic and molecular level, as well as to develop molecular-based strategies for diagnosis and treatment. 

From the seminal paper of Linus Pauling on sickle cell anemia to the recent genomic studies on gliomas, the Molecular BioMedicine field has been expanding, thanks in part to the development of computational methods. 

This course (in English) will introduce basic concepts of Computational Molecular BioMedicine, covering topics such as homology modeling, AI-based structural prediction, molecular docking, cofolding methods, drug design and molecular dynamics simulations. 

In addition, it will present freely available computational tools, webservers and databases commonly used in the field. 

The theoretical concepts will be exemplified by case studies, mostly drawn from Neuromedicine. 

Relevant literature and documentation will be provided, as well as the slides of the lectures.

Some overarching links can be found below:

•  Molecular Medicine - To be or not to be (Link)

•  Protein Data Bank (PDB): Molecule of the Month & Educational Resources.

•  Visual Molecular Dynamics (VMD): Gallery of Images & Movies.

•  Books (available at the ULB):

  •  "Molecular Modelling: principles and applications". Andrew R. Leach, Prentice Hall (2001).

  •  "Molecular Modeling and Simulation: an interdisciplinary guide". Tamar Schlick, Springer (2010).

  •  "From Protein Structure to Function with Bioinformatics". Daniel J. Ridgen, Springer (2017).

  •  "Wirkstoffdesign Entwurf und Wirkung von Arzneistoffen".  Gerhard Klebe,  Springer (2023).

  •  "Drug Design From Structure and Mode-of-Action to Rational Design Concepts". Gerhard Klebe,  Springer (2024).

01. Introduction to Molecular Biomedicine

• Molecular Medicine: Definition & History

• The computational microscope

• Examples

Link:  Molecular Medicine in Wikipedia

Image credit: TCBG at Univ. of Illinois Urbana-Champaign

02. Structure of biomolecules

• Basics of protein structure

• Basic of protein-ligand interactions 

Link: PDB101 - What is a protein?

Image credit: Howarth's alphabet

03.  Online Databases

• Molecular basis of disease

• Molecular basis of drug effects

• Molecular basis of drug side effects

• Protein databases: UniProt and Protein Data Bank (PDB)

• Ligand databases: DrugBank and PubChem

Links: UniProt, Protein Data Bank, DrugBank and PubChem

Image credit: PDB-101

04. Protein Structure Modeling

• Experimental structural methods

• Homology modeling

• AI-based structural prediction

• SwissModel webserver

• AlphaFold Protein Structure Database

Links:  SwissModel and AlphaFold

Image credit: PDB-101

05. Protein Structure Modeling Examples

• GABA receptors and Molecular Medicine

• Oxytocin receptor and Autism-linked mutations

Links:  SwissModel and AlphaFold

Image credit: University of Lausanne

06. Protein-Ligand Complex Modeling

• Protein-ligand docking

• Co-folding methods

• Webservers: SwissDock and HADDOCK.

Links:  SwissDock and HADDOCK 

Image credit: Wikipedia

07. Protein-Ligand Complex Modeling Examples

• Bitter taste receptors and Asthma treatment

• Isocitrate Dehydrogenase and Glioma-associated mutations

• GABA receptors and Photopharmacology

Links:  SwissDock and HADDOCK 

Image credit:  GOMoDo

08. Drug Design

• Introduction to rational drug design

• Computer-Aided Drug Design

• Prediction of ADMET properties

Links: Klebe's Drug Design

Image credit: Chodera Lab

08. Drug Design Examples

• Antiinflammatory drugs

• Drugs against melanoma

• Cancer immunotherapy

Links: Drug Design Workshop

Image credit: Röhrig et al. J. Med. Chem. (2015)

09. Molecular Dynamics Simulations

• Introduction to Molecular Dynamics

• Molecular Dynamics For All: Folding@home and GPUGrid

• Molecular Dynamics Examples: Quantum Mechanics, Molecular Mechanics, Coarse Grained

Links: Folding@home and GPUGrid

Image credit: Beckstein Lab

10. Molecular Dynamics & Disease-linked Mutations 

• Databases of disease-linked genetic variants

       Links: OMIM, dSysMap and UniProt

• Webservers to assess the effects of mutations on protein stability, interactions and dynamics

       Links:  DUET, MutaBind2 and DynaMut 

• Examples: Cone-rod dystrophy and Early-onset Parkinson's disease

Image credit: NIH-National Cancer Institute

11. Molecular Dynamics & Drug Design

• Improving/Refining Molecular Docking results

• Calculating Drug Binding Energy & Kinetics

• Examples

Image credit: Iglesias et al. WIRES Comput. Molec. Sci. (2018)

12. Molecular Dynamics & Mutation Effects

• Understanding the effect of Drug-Resistant Mutations

• Predicting the effect of Disease-linked Mutations

• Examples

Image credit: Molecular Dynamics Movies from the TCBG at UIUC

13. Protein-Protein Complex Modeling

• Protein-protein docking

• AI-based protein-protein complex prediction

• Protein-protein interaction networks

Links: HADDOCK and AlphaFold Multimers

Image credit: ZBI at University of Saarland