Teaching
Computational Molecular BioMedicine - WiSe 2023/2024
Wahlfach (Q1+Q2) der Medizinischen Fakultät der HHU Düsseldorf
Dozentin: Dr. Mercedes Alfonso-Prieto
Email:
alfonsop_at_hhu.de
m.alfonso-prieto_at_fz-juelich.de
Tag: Mittwoch
Zeit: 15:00 – 16:30 Uhr
Rhythmus: wöch. 11.10.2023 bis 07.02.2024 (Vorlesung fällt am 01.11.2023 aus!)
Raum: Hörsaal Frauenklinik (Geb. 14.75)
Vorlesungssprache: Englisch
Prüfungsleistung:
Teilnahme ist ausreichend.
Die Prüfung ist nicht obligatorisch, aber nach Absprache möglich (wenn Sie ein benotetes Wahlfach wünschen).
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 bioinformatics, structural modeling, molecular docking, drug design and molecular dynamics simulations.
In addition, it will present freely available computational tools and webservers commonly used in the field.
The theoretical concepts will be exemplified by case studies, mostly drawn from Neuromedicine.
* Preliminary Literature & Documentation *
Relevant literature and documentation will be provided, as well as the slides of the lectures.
Some general links can be found below:
- Molecular Medicine - To be or not to be (Link)
- Protein Data Bank: Molecule of the Month & Educational Resources.
- VMD: Gallery of Images & Movies.
- "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).
* Rough Syllabus *
Stand: Juni 2022
01. Introduction to Molecular Biomedicine
Definition of Molecular Biomedicine.
The computational microscope
Examples.
Links: Molecular Medicine in Wikipedia
Image credit: TCBG at Univ. of Illinois Urbana-Champaign
02. Structure of biomolecules
Introduction to protein structure.
Structure databases: Protein Data Bank (PDB) and PDBSum.
Links: Protein Data Bank and PDBSum
Image credit: Howarth's alphabet
04. Methods for Structural Determination
Introduction to experimental structural methods: X-ray crystallography, NMR and cryo-EM
Homology modeling.
AI-based structural prediction.
Online modeling webservers: SwissModel and GOMoDo.
AlphaFold Protein Structure Database.
Links: SwissModel and GOMoDo webservers; AlphaFold Protein Structure database
Image credit: PDB-101
05. Homology Modeling Examples
Glioma and Isocitrate Dehydrogenase
Neuropsychiatric diseases and Ligand-Gated Ion Channels
G-Protein Coupled Receptors
Links: SwissModel and GOMoDo webservers
Image credit: University of Lausanne
08. Drug Design
Introduction to rational drug design.
Computer-Aided Drug Design
Prediction of ADMET properties
Links: Drug Design Workshop
Image credit: Röhrig et al. J. Med. Chem. (2015)
09. Molecular docking: Protein-Protein
Introduction to protein-protein docking.
Online docking webservers: HADDOCK.
Protein-protein interaction networks
Links: HADDOCK webserver
Image credit: ZIB at University of Saarland
10. Disease-linked Mutations
Databases of disease-linked genetic variants: OMIM, dSysMap and UniProt
Effects of mutations on protein stability
Effects of mutations on protein interactions: Hotspots
Effects of mutations on protein dynamics
Examples: Cone-rod dystrophy and Early-onset Parkinson's disease
Links: OMIM and dSysMap databases
Links: Elaspic , MutaBind and DynaMut webservers
Image credit: NIH-National Cancer Institute
11. Molecular Dynamics: Basics
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; Molecular Dynamics Movies from the TCBG at UIUC
Image credit: Beckstein Lab
12. Molecular Dynamics & Disease-Linked Mutations
Predicting the effect of disease-linked mutations comparing MD simulations of wild-type protein and mutant variant(s)
Examples
Image credit: Molecular Dynamics Movies from the TCBG at UIUC
13. Molecular Dynamics & Drug Design
Improving/Refining Molecular Docking results
Calculating Drug Binding Energy & Kinetics
Understanding Drug-Resistant Mutations
Image credit: Iglesias et al. WIRES Comput. Molec. Sci. (2018)
14. Molecular Dynamics: Online Resources
Databases of simulation data: MoDEL, MemProtMD, GPCRmd, Dynameomics and BigNASim.
Webtools to setup molecular dynamics simulations: MDWeb and CHARMM-GUI.
Links: MoDEL, MemProtMD, GPCRmd, Dynameomics and BigNASim; MDWeb and CHARMM-GUI.
Image credit: Beckstein Lab