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Principles of Fragment Based DrugDiscovery, 1.5 credits

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This course syllabus was confirmed by The Research Programmes Board at the Faculty of Science 30 October 2023. The course is in the third cycle and amounts to 1.5 credits.
The course syllabus is formally approved in Swedish. This is a translation.

Learning outcomes

The course aims to introduce participants to fragment-based lead discovery, which is an approach to discover small molecule compounds binding a target protein of medical interest and then further use that information to develop potential therapeutic compounds. The process includes biophysical techniques as well as structural biology methods such as X-ray crystallography and computational chemistry. Participants will learn the theory of the whole process of fragment-based lead development, will be introduced to available relevant national and international infrastructures and will learn about sample preparation and data collection. Furthermore, the participants will work individually with structural models and learn about X-ray data processing and analysis.
On completion of the course, participants shall be able to:

Knowledge and understanding

Explain what biophysical methods are used in fragment-based drug discovery.
Explain what strategies are used in fragment elaboration and evaluation.
Identify what infrastructures can be used for a specific problem in drug discovery.
Explain how X-ray crystallography is used for fragment screening.

Competens and skills

Use molecular visualization and modelling software for initial analysis of the protein structure.
Analyse molecular details of fragment-protein complexes and identify key interactions.

Judgement and approach

Critically evaluate structural models and judge the quality of the data.
Evaluate the results of fragment screening and estimate possible further screening strategies.

Course content

The course consists of lectures, practical exercises and workshops, individual work and preparation of a presentation.
Part 1:

Symposium with invited speakers presenting current research in the field.
Lectures covering relevant topics in the field:
- Biophysical methods (WAC [weak affinity chromatography], NMR, SPR).
- Strategies in medicinal chemistry and SAR studies
- Principles of ADMET analysis
- Necessary infrastructure
Lectures on how X-ray crystallography is used in fragment screening and introduction to other structural methods relevant for drug discovery (serial crystallography, neutron crystallography and cryo-EM).

Part 2:

Visit to MAX IV with demonstration of protein crystal handling, X-ray data acquisition and analysis.
Workshop on structural models and computational chemistry methods for fragment analysis and development.Forms of instructions

The course consists of lectures, seminars, performance of an experiment and to a large extent of practical analysis work. It is compulsory to participate in 80% of the lectures and to participate in the final seminar.

Forms of instruction

The course consists of lectures, workshops and practical exercises where participants work in groups and learn how to use different software and analyse data, and participate in a practical demonstration on data collection. Participation in all sessions is mandatory.

Forms of assessment

The assessment is based on active participation throughout the course and an individual oral presentation of group work with structural data. Each presentation is prepared by a group of 3-4 students.

Grades

Possible grades are Pass and Fail. For a grade of Pass, the student must attend the entire course and give an approved oral presentation after group work.

Language of instruction

The course is given in English.

Necessary prior knowledge

-

Additional information

The course is organized by the LINXS (Lund Institute of Advanced Neutron and X-ray Science) working group on structure-based drug design within the theme of Integrative Pharmacology and Drug Discovery.

Course responsible teacher and unit/division

Raminta Venskutonyte
Email: raminta.venskutonyte@med.lu.se

The Division of Biochemistry and Structural Biology

Do you have questions? Please contact FUstudierektor@kilu.lu.se