The course concerns both the fundamentals and several modern bio-medical applications of Molecular Modelling. We discuss Molecular dynamics, Quantitative Structure Activity Relations, Monte Carlo methods, and statistical thermodynamic approaches. As demonstration studies, we will work on realistic biomedical cases inspired by companies from the Leiden Science park: (a) the development of blood-brain barrier crossing using modified vesicles (to-BBB), (b) the development of polynucleotide agents for fighting Duchenne’s disease (Prosensa), and © screening protein-ligand interactions for accelerated drug discovery (Zobio). In all cases a computer model could be of great help in reducing time-consuming experiments, but then there are always several interwoven challenges that one needs to face. For example, if one makes the molecular model more accurate, with more detail, it becomes slow; perhaps too slow to be of practical us; or, in many cases one has good insight into the molecule of interest (medicine or active), but then the (bio)environment or toxicity is only poorly understood.
The course assumes a working knowledge of the modeling platform CULGI; this can be obtained either by self-study prior to the course, or by following the course Molecular Modeling (MST/Minor).
CULGI is installed on LCP computers, and can additionally be downloaded for personal use. Additional materials will be handed to the students during the course.
Visit to (one of) the companies from the case studies will be part of the course: a good way to scout for a challenging internship.
The course is organized as a series of tasks, that are discussed informally in the office of the instructor.
H.J.C. Berendsen, “Simulating the Physical World”; Culgi modeling software package. Both book and software will be made available to the students.
The exam is by reporting on a final assignment.