Høst 2018

KJE-8704 BIOSTRUCT - Structure guided drug discovery and design - 5 stp

The course is administrated by

Institutt for kjemi

Type of course

Theoretical and practical subject. The course is offered on condition that a minimum number of students register for the course.

Course contents

This course reviews how modern drug discovery increasingly includes a diverse range of tasks that benefit from the knowledge of the atomic structures of drug binding sites and their interactions with drugs. International and internal speakers will review: retrospective studies on the structural mechanisms of classical drugs, structures of drug target classes, evaluation of drug-ability, de-novo and substrate based hit generation, structure guided screen design, scaffold swapping, in vitro and in silico binding site characterization (fragment/solvent screens, cheminformatic fragmentization), lead optimization, structure guided synthesis strategies (hit explosion, diversity oriented synthesis), and late stage processes, including prediction of and reaction to drug resistance. Presentation of these topics aims to remain fundamentally grounded in the basic chemistry of protein-ligand interactions, chemical reactivity in biological environments, chemical synthetic methods, enzyme kinetics, thermodynamics and cheminformatics. Lectures will be accompanied by computer and literature exercises, and students will propose and follow up with a project, optionally integrated with their thesis research. The candidate will acquire experience with a diverse range computer-based tasks relevant to target structure based drug design. The topics include target structure evaluation, hit characterization, data mining and multidimensional analysis, and the selection of synthetic approaches to generate chemical libraries. This learning will be expanded in depth by application to the specific research interests of the student in a research proposal and report to be completed following the course.

Application deadline

Registration deadline for PhD students at UiT - The Arctic University of Norway: September 1st for autumn semester and February 1st for spring semester.

Application deadline for other applicants: June 1st for autumn semester and December 1st for spring semester. Application code 9303 in Søknadsweb.

Admission requirements

PhD students or holders of a Norwegian master´s degree of five years or 3+ 2 years (or equivalent) may be admitted. PhD students must upload a document from their university stating that there are registered PhD students. This group of applicants does not have to prove English proficiency and are exempt from semester fee. Holders of a Master´s degree must upload a Master´s Diploma with Diploma Supplement / English translation of the diploma. Applicants from listed countries must document proficiency in English. To find out if this applies to you see the following list: Proficiency in English must be documented - list of countries For more information on accepted English proficiency tests and scores, as well as exemptions from the English proficiency tests, please see the following document: Proficiency in english - PhD level studies

Students should have some knowledge in organic chemistry and biochemistry.

PhD students at UiT The Arctic University of Norway register for the course through StudentWeb. Other applicants apply for admission through SøknadsWeb. Applicants must attach a confirmation of their status as a PhD student from their home institution. Students who hold a Master of Science degree, but are not yet enrolled as a PhD-student have to attach a copy of their master's degree diploma. These students are also required to pay the semester fee. More information regarding PhD courses at the Faculty of Science and Technology is found here.

Objective of the course

Knowledge

Properties of drugs and drug targets

Has an overview of the major drug target types
Has an overview of basic drug properties
Has an overview of the basic physics and chemistry of drug-target interactions
Has an overview of target-based drug resistance mechanisms

Biophysical methods and screening

Has an overview of the major methods to evaluate drug-target interactions
Has an overview of biochemical and cellular methods to screen for hits
Has an overview of theoretical and experimental fragment methods

Workflows

Has knowledge about how structure based drug discovery methods are implemented in industry
Has an overview on drug approval processes

Data mining and cheminformatics

Has knowledge about methods and databases for chemical information searching
Has insight into applications of multidimensional statistical analyses

Synthetic medicinal chemistry

Has knowledge about "hit explosion" strategies for the generation of drug lead series
Has knowledge about the use of "diversity-oriented synthesis" to generate suitable chemical libraries

Skills

Can use molecular graphics to visualize drug target structures
Can perform computer-based analyses of key drug target properties, such as drug-ability
Can perform computer-based analyses of key drug properties, such as the Pfizer rules.
Can perform computer-based analyses of the properties of a series of hit compounds, such as clustering and pharmacophore generation
Can conduct searches in chemical databases
Can create a strategy to initiate screening
Can create in-silico a focussed library of potential hit/lead compounds based on a set of known synthetic methods

General competence

Understands how drug and drug target structures are used across the drug design process
Can advise on drug discovery strategies

Language of instruction

The language of instruction is English and all of the syllabus material is in English. Examination questions will be given in English

Teaching methods

Lectures: 15 h, Practical sessions: 30 h PC-based exercises

Assessment

A research proposal will be written based on course skill and research interests; a report will be written describing the results of that research. Pass/fail grades will be assigned according to the assessment of the quality of the research proposal (10%), research report (50%), and final oral examination after submission of the report (40%).