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Protein Folding, Misfolding and Design (PFMD)


Admission requirements

Elective course MSc Chemistry, MSc Life Science and Technology.
Students with a BSc MST/LST or equivalent. Students with a BSc in other subjects should have knowledge of amino acids and protein structure.

A similar course was previously given under the name Design and Self-assembly of Biomolecules (DSB), uSis code 4423DSBIO. This course cannot be combined with DSB in a programme.


This course is intended to give students an insight into the fundamentals of protein folding, how these principles may be exploited to design new proteins with novel functions, and how protein misfolding can lead to disease. A brief recap of protein structure will be given, before the so-called ‘protein folding problem’ will be explained. Key differences between folding in the test tube and the cellular environment will be highlighted. Cellular strategies to assist protein folding and combat protein misfolding will be explored through case studies of the molecular chaperones Trigger Factor, Hsp70 and GroEL.
The course will then focus on how, and why, researchers design peptides and proteins. Design principles for small peptides will be explained, as will strategies for how these peptides can be programmed to self-assemble. Three different protein design strategies: de novo design (bottom-up design), protein redesign (top-down design), and computational design will also be discussed.
Finally, the course will wrap up by addressing the risks associated with protein misfolding. With the help of recent literature, we will study examples of human diseases linked to protein misfolding and aggregation (Creutzfeldt-Jakob disease, Alzheimer’s disease, cystic fibrosis,…) and therapeutic strategies to slow or reverse these processes.
Note that due to a change in personnel, the course will this year focus primarily on protein folding, misfolding and disease with a reduced emphasis on protein design.

Course Objectives

At the end of this course students will be able to:

  • Design elements of protein secondary structure such as α-helices and β-strands.

  • Derive from case-studies from the literature, how peptides and proteins can be programmed to self-assemble to form higher-order structures, and what kinds of functions such structures can fulfil.

  • Weigh the advantages and disadvantages of de novo design, protein redesign, and computational design in creating new protein structures with novel functions.

  • Contrast in vitro protein folding and folding in the cell.

  • Compare the mechanism of action of different families of molecular chaperones.

  • Explain how protein misfolding can lead to disease and identify appropriate therapeutic strategies to intervene in this process.

  • Select appropriate analytical techniques to characterize peptide/protein structures and investigate pathological protein aggregation.

  • Critically evaluate a research papers and present this to the group.


Schedule information can be found on the website of the programmes.

You will find the timetables for all courses and degree programmes of Leiden University in the tool MyTimetable (login). Any teaching activities that you have sucessfully registered for in MyStudyMap will automatically be displayed in MyTimeTable. Any timetables that you add manually, will be saved and automatically displayed the next time you sign in.

MyTimetable allows you to integrate your timetable with your calendar apps such as Outlook, Google Calendar, Apple Calendar and other calendar apps on your smartphone. Any timetable changes will be automatically synced with your calendar. If you wish, you can also receive an email notification of the change. You can turn notifications on in ‘Settings’ (after login).

For more information, watch the video or go the the 'help-page' in MyTimetable.

Mode of instruction

Lectures and literature discussion sessions. Students will give presentations in small groups on a relevant literature paper selected from a list provided.

Assessment method

Written exam (70%), a group presentation on a relevant literature paper (25%), and a computer-based assignment (5%).

Reading list

All relevant literature will be provided on Brightspace at least seven days before the relevant lecture. Students will benefit from reading, in advance, the papers that will be discussed during the lectures.


From the academic year 2022-2023 on every student has to register for courses with the new enrollment tool MyStudyMap. There are two registration periods per year: registration for the fall semester opens in July and registration for the spring semester opens in December. Please see this page for more information.

Please note that it is compulsory to both preregister and confirm your participation for every exam and retake. Not being registered for a course means that you are not allowed to participate in the final exam of the course. Confirming your exam participation is possible until ten days before the exam.

Extensive FAQ's on MyStudymap can be found here.


Dr. A.S. Wentink


Assignment deadlines are communicated via Brightspace.

According to OER article 4.8, students are entitled to view their marked examination for a period of 30 days following the publication of the results of a written examination. Students should contact the lecturer to make an appointment for such an inspection session.