[SDD] Structure-based Drug Design

[SDD] Structure-based Drug Design

Post Genome Challenge: Structure Based Drug Design

This course will provide an understanding of the following:

  • the relationship between the physicochemical characteristics of a protein and its three-dimensional structure.
  • a structural perspective of the mechanism of protease substrate hydrolysis.
  • kinetic and structural implications of anion activation.
  • an introduction to drug discovery and protein structure-based drug design.

Lecturer

Dr Edward Sturrock, Department of Medical Biochemistry, will present lectures on the post genome challenge showing how our increasing genomic knowledge needs to be integrated with structural information and he will present seminars on drug design. Dr Sturrock is actively involved in structural biology research leading directly to the rational design of drugs and work done in his laboratory is a major motivating factor for the establishment of this programme.


Syllabus

  1. The renin-angiotensin system and the ACE in the hole
    • The components of the RAS.
    • Gene and protein organisation of ACE.
    • Towards an x-ray crystal structure: Overcoming the glycosylation problem.
  2. The structure of angiotensin-converting enzyme and mechanism of substrate hydrolysis.
  3. Chloride activation of angiotensin converting enzyme
    • Arg(1098) is critical for the chloride dependence of human ACE C-domain catalytic activity. Insights from mutagenesis and kinetic studies.
    • Structural insights into anion activation.
  4. Drug discovery
    • An introduction to drug discovery and structure-based drug design.
    • Gene duplication: A structural basis for improved drug selectivity and side. effect profiles.
    • Structure based drug design. COX 2 inhibitors: A case study.