Structure-based Drug Research

Course content

In modern drug research the focus is on analysis and optimization of the interactions between the drug and the specific target. This course focuses on essential experimental and computational methods for analyses of target proteins and their interactions with drugs or drug-like molecules.

The course is divided into eight modules introducing different methods and how to use the results in structure-based drug design of small molecules and biopharmaceuticals. In the lectures, the students are introduced to the fundamental principles behind the methods and exercises will provide the students with hands-on experience. 

The course will cover the following:

  • Molecular mechanics based methods and conformational analysis of small molecule drugs
  • Modelling and engineering of target proteins
  • Protein structure determination using X-ray crystallography and single particle electron microscopy
  • Analysis of protein targets and their formulation in solution using small angle X-ray scattering (SAXS)
  • Creation and use of ligand-based pharmacophore models in drug design
  • Identification of drug candidates through docking of small molecules into the binding site of the protein target
  • Analysis of interactions between protein targets and small molecule drugs/biopharmaceuticals for structure-based drug design

 

This course is relevant for students interested in the drug research area and other areas where it is important to:

  • have knowledge about experimental and theoretical methods that can be used to analyze molecular characteristics of biologically important molecules
  • understand the interactions between ligands and biomacromolecules
  • get hands-on experience with modern tools in experimental and theoretical molecular modeling
Education

MSc Programme in Medicinal Chemistry - compulsory

MSc Programme in Pharmacy (Danish programme cand.pharm) - elective

MSc Programme in Pharmaceutical Sciences (Danish programme cand.scient.pharm) - restricted elective

MSc Programme in Pharmaceutical Sciences (English programme) - restricted elective

 

Learning outcome

The course objective is to provide the students with knowledge and competences within experimental and computational methods for structure-based drug research. This includes analyses of small molecule drugs and biopharmaceuticals, as well as their interactions with relevant target proteins.

 

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

Knowledge

  • know advanced concepts of interactions between protein targets and small molecule drugs/biopharmaceuticals
  • know the principles and methods used for rational design of drugs
  • understand advantages and limitations of the methods used in structure-based drug design

 

Skills

  • apply state of the art methods in experimental structure analysis (protein crystallography, SAXS, electron microscopy)
  • extract relevant information from 3D structural models (experimental or theoretical)
  • apply appropriate computer-based tools in modern drug research (e.g. ligand docking, pharmacophore models)

 

Competences

  • select the most appropriate experimental method and computer-based tools for drug design and discovery
  • use and critically evaluate results achieved from experimental structural analyses of proteins and drugs
  • use and critically evaluate results obtained with computer-based methods for structure-based design of drugs

The course will comprise 8 modules, introducing experimental and computational methods with focus on different aspects of structure-based drug research.

The structure for a module will be:
Monday: 1 introductory lecture
Wednesday: 2 lectures + exercises
Monday (following week): Student presentations and summarizing wrap-up

From Monday to Wednesday, the students can prepare for the upcoming exercises. Wednesday to Monday, the students are expected to finalize exercise work and to prepare for the presentations Monday afternoon.

• Lectures: 24 hours
• Computer exercises: 40 hours
• Student presentations: 24 hours
• Preparation: 115 hours
• Exam: 3 hours

Total: 206 hours

  • Reviews and scientific papers available at the course homepage
  • Supplementary notes (notes with additional information on methods used – to be downloaded from course homepage)

Teaching is organized on the assumption that students have already acquired knowledge in medicinal and biostructural chemistry, including protein structures, biophysical techniques, protein-ligand interactions, and basic organic and physical chemistry. No special skills for computer programming are needed. Software with graphical user interfaces will be used.

Continuous feedback during the course of the semester

Exercises: Each exercise module will be concluded with selected student presentations with feedback and discussion.

Lectures: Digital quizzes are used as a supplement to the modules.

ECTS
7,5 ECTS
Type of assessment
Written examination, 3 hours under invigilation
The examination assignment typically consist of 3 assignments each with 5 sub-assignments. For each sub-assignment at least 3 possible answers are provided in a multiple choice format. Typically the 3 assignments deal with experimental protein structure determination and analysis; small-molecule drug candidates; and interactions between protein targets and small molecule drugs/​biopharmaceuticals, respectively.
Aid
Written aids allowed

There is access to the following at the exam on Peter Bangs Vej:

  • MathType formel programme
  • Maple

 

USB access – for usb stick with notes

Marking scale
7-point grading scale
Censorship form
No external censorship
Criteria for exam assessment

To achieve the grade 12 the student must be able to:

Knowledge

  • know advanced concepts of interactions between protein targets and small molecule drugs/biopharmaceuticals
  • know the principles and methods used for rational design of drugs
  • understand advantages and limitations of the methods used in structure-based drug design

 

Skills

  • apply state of the art methods in experimental structure analysis (protein crystallography, SAXS, electron microscopy)
  • extract relevant information from 3D structural models (experimental or theoretical)
  • apply appropriate computer-based tools in modern drug research (e.g. ligand docking, pharmacophore models)

 

Competences

  • select the most appropriate experimental method and computer-based tools for drug design and discovery
  • use and critically evaluate results achieved from experimental structural analyses of proteins and drugs
  • use and critically evaluate results obtained with computer-based methods for structure-based design of drugs
  • Category
  • Hours
  • Lectures
  • 24
  • Exercises
  • 40
  • Project work
  • 24
  • Preparation
  • 115
  • Exam
  • 3
  • English
  • 206