Postgraduate

CHY8825 : Proteins as Drug Targets: structure, function, and molecular modelling

Semesters
Semester 1 Credit Value: 10
ECTS Credits: 5.0

Aims

The purpose of this course is to equip students with solid foundations in structural biology, protein biochemistry, and proteins as drug targets – from principles governing protein structure and dynamics, drug-protein interactions, through pharmacology, to modern methods in protein structure prediction and protein simulations. This will be organised in two thematic blocks.

The first one will focus on key concepts of molecular pharmacology and elements of protein biochemistry, cell and molecular biology, relevant in the context of modern drug chemistry. Students will learn about relationships between ligand-receptor interactions and protein structure, signal transduction in relationship to the cell anatomy and fundamental biochemistry, and molecular pharmacology of different classes of receptors, ion channels, and enzymes. Students will also learn about the methodology of preclinical studies and clinical trials. Additionally, students learn about the pharmacology of CNS, cardiovascular, and immune systems, linking physiology, cell biology, biochemistry, molecular pharmacology, and medicinal chemistry.

The second block is intended to make students familiar with the basic terminology, key concepts, data formats and algorithms of modern protein modelling and simulation methods. This will include structure prediction using homology and ab initio protein modelling, building protein-ligand and protein-protein complexes and fitting the atomistic data to lower-resolution sets. The students will be taught about the establishment of intellectual property through modelling techniques. During this part of the course, students will also learn techniques suitable for visualising macromolecular data using the open-source as well as proprietary software packages.

Outline Of Syllabus

Introduction to macromolecules, drug-receptor interactions and molecular pharmacology
Dr. Agnieszka K. Bronowska

• Key elements of biochemistry: proteins, peptides, nucleic acids, lipids, and small molecules
• Important metabolic pathways
• Foundations of cell biology: anatomy of the cell, structure and functions of cellular organellae and their compartments
• Receptor-ligand interactions and protein structure
• Principles of thermodynamics in drug chemistry context
• Signal transduction and modulation
• Pharmacokinetics and pharmacodynamics
• Molecular pharmacology of receptors, channels and enzymes
• Pharmacology of the immune system: molecular basis of inflammation
• Before the molecule becomes a drug: methods in preclinical studies
• An overview of clinical trials
• Case Studies 1

Introduction to macromolecular modelling
Dr. Agnieszka K. Bronowska

• Key concepts, tools and techniques
• Classical mechanical force fields
• Modelling of proteins
• Sequence alignments and sequence homology
• Homology modelling
• Molecular docking
• Energy minimisation
• Molecular dynamics simulations
• Data analysis
• Beyond all-atom molecular mechanics: coarse-grain and QM/MM simulations
• Case Studies 2

Teaching Methods

Please note that module leaders are reviewing the module teaching and assessment methods for Semester 2 modules, in light of the Covid-19 restrictions. There may also be a few further changes to Semester 1 modules. Final information will be available by the end of August 2020 in for Semester 1 modules and the end of October 2020 for Semester 2 modules.

Teaching Activities
Category Activity Number Length Student Hours Comment
Guided Independent StudyAssessment preparation and completion21:002:00Synchronous dry lab
Structured Guided LearningLecture materials22:004:00Online module content
Guided Independent StudyAssessment preparation and completion120:0020:00Revision for alternate assessment
Scheduled Learning And Teaching ActivitiesPractical12:002:00Synchronous dry labs
Structured Guided LearningAcademic skills activities21:002:00Online dry lab
Scheduled Learning And Teaching ActivitiesWorkshops21:002:00One workshop for each thematic band - AKB
Guided Independent StudyIndependent study120:0020:00Skills practice for dry labs
Guided Independent StudyIndependent study136:0036:00Background reading and practice exam questions
Scheduled Learning And Teaching ActivitiesModule talk121:0012:00Synchronous online module talks - AKB
Total100:00
Teaching Rationale And Relationship

N/A

Assessment Methods

Please note that module leaders are reviewing the module teaching and assessment methods for Semester 2 modules, in light of the Covid-19 restrictions. There may also be a few further changes to Semester 1 modules. Final information will be available by the end of August 2020 in for Semester 1 modules and the end of October 2020 for Semester 2 modules.

The format of resits will be determined by the Board of Examiners

Other Assessment
Description Semester When Set Percentage Comment
Written exercise1M40Assessment of practical work performed in dry labs
Computer assessment1M60Alternate end of module assessment
Assessment Rationale And Relationship

The alternate assessment will test the student’s knowledge and understanding of the coursework. The in course assessment will test information literacy and presentation skills.

Study Abroad students may request to take their exam before the semester 1 exam period, in which case the format of the paper may differ from that shown in the MOF. Study Abroad students should contact the school to discuss this.

Reading Lists

Timetable