CH412-15 Advanced Biophysical Chemistry

Department: Chemistry
Level: Undergraduate Level 4
Module leader: Rebecca Notman
Credit value: 15
Module duration: 10 weeks
Assessment: 30% coursework, 70% exam
Study location: University of Warwick main campus, Coventry

Introductory description

N/A

Module aims

The aim of the module is to describe computational and experimental methods used in physical chemistry and their application to study the structure and dynamics of biological molecules.

The module also aims to provide hands-on experience of performing quantitative analysis of experimental data and practical computational calculations.

The module is divided into three Parts, of which two may be chosen for 15 CATS. These are:

Part 1: Structural biology by X-ray crystallography
This part of the module introduces X-ray crystallography as a tool to understand protein structure. It will provide an overview of the principles of X-ray crystallography, the practicalities of structure determination and how to assess structure quality. The module will also emphasise how X-ray crystal structures of proteins can give insight into enzyme mechanism and guide drug design.

Part 2: Biomolecular simulation
This part module builds on aspects of theoretical and computational chemistry introduced in the earlier years of the MChem course. A number of methods in molecular simulation and their theoretical foundations will be presented. There will be an emphasis on approaches used to probe biological phenomena and calculations of properties pertinent to biological systems.

Part 3: Structural biology by NMR
This part module describes current use of solution state NMR to understand biomolecular structure and interactions, and builds on materials covered in Years 2 and 3. The focus of the materials covered here is the elucidation of biomolecular structure and ligand-binding properties for biomolecules across a range of sizes. Students will also obtain practical experience of NMR data interpretation in a workshop.

Outline syllabus

This is an indicative module outline only to give an indication of the sort of topics that may be covered. Actual sessions held may differ.

Part 1: Structural biology by X-ray crystallography
Principles of crystallography and crystallisation techniques
Overview of methods to solve the phase problem, including isomorphous replacement, anomalous diffraction and molecular replacement
Using the suite of software in cpp4 to solve and refine a protein structure with a bound ligand by molecular replacement, and analyse the accuracy and quality of the structure
Using protein crystal structures to obtain information about enzyme mechanism or guide drug discovery, using latest literature examples.

Part 2: Biomolecular simulation
Review of molecular dynamics and Monte Carlo methods.
Force fields for biomolecular simulation.
Free energy calculations. Thermodynamic integration and perturbation; potentials of mean force.
Advanced sampling. Biased sampling methods, replica exchange molecular dynamics.
Coarse-graining.
Calculated properties. Energetics, structure and dynamics; relationship to experimentally determined quantities.

Part 3: Structural biology by NMR
Introduction to structural biology. Structure activity relationships; ligand binding and design; protein-protein interactions; physical chemistry of biomolecular systems. How does NMR contribute to our understanding of biomolecular structure – i.e. what kinds of things can we learn using NMR?
Small biomolecules. Homonuclear 2D NMR methods (i.e. TOCSY, NOESY and ROESY); linking data to polypeptide structure (assignment); case studies emphasizing the important biological roles of peptides.
Mid-sized proteins. Heteronuclear 2D and 3D NMR methods (e.g. HSQC and hybrid techniques); deuterium exchange; paramagnetic relaxation enhancement.
Large proteins. Triple resonance experiments/3D NMR methods; 3D NMR experiments; sensitivity issues; selective labelling and unlabelling methods; TROSY methods.
Very large proteins and complexes. Indirect NMR methods for investigating ligand binding. E.g. STD-NMR, DOSY.

Learning outcomes

By the end of the module, students should be able to:

Students will be able to describe and evaluate the roles that a selection of experimental and computational methods used in physical chemistry play in solving biological problems.
Students will be able to analyse data from experiments involving biological molecules and perform and analyse computational calculations.

Indicative reading list

Part 1: X-ray crystallography

Jan Drenth, Principles of Protein X-ray Crystallography
Gale Rhodes, Crystallography made crystal clear
A selection of papers from the recent research literature, that may change from year to year, will also be provided.

Part 2: Biomolecular simulation

A.R. Leach, Molecular Modelling: principles and applications, Longman (1996).
M.A. Allen and D.J. Tildesley, Computer Simulation of Liquds, Oxford University Press (2017).
A selection of papers from the recent research literature, that may change from year to year, will also be provided.

Part 3: Structural biology by NMR

Sanders, J.K.M. and Hunter, B.K., Modern NMR Spectroscopy: A Guide for Chemists.
Zerbe, O. and Jurt, S., Applied NMR Spectroscopy for Chemists and Life Scientists
Cavanagh, J., Fairbrother, W.J., Palmer, A.G., Rance, M., and Skelton, N.J., Protein NMR Spectroscopy: Principles and Practice.
Or any other book on Protein NMR Spectroscopy available from the library.

Subject specific skills

Problem solving
Written communication
Oral communication

Transferable skills

Problem solving
Written communication
Oral communication

Study time

Type	Required
Lectures	12 sessions of 1 hour (8%)
Practical classes	4 sessions of 1 hour (3%)
Private study	134 hours (89%)
Total	150 hours

Private study description

N/A

Costs

No further costs have been identified for this module.

You do not need to pass all assessment components to pass the module.

Students can register for this module without taking any assessment.

Assessment group D3

	Weighting	Eligible for self-certification
Assessment component
Workshop Reports	30%	Yes (extension)
2 x workshop reports (15% each)
Reassessment component is the same
Assessment component
In-person Examination	70%	No
Answerbook Pink (12 page) Periodic Tables Students may use a calculator
Reassessment component is the same

Feedback on assessment

Workshop reports marked by academic staff, written feedback within 20 days. Cohort level exam feedback provided via Moodle.

Past exam papers for CH412

Pre-requisites

To take this module, you must have passed:

Any of

Courses

This module is Optional for:

Year 1 of TCHA-F1PB MSc in Chemistry with Scientific Writing
Year 1 of TCHA-F1PE Postgraduate Taught Scientific Research and Communication
UCHA-F110 Undergraduate Master of Chemistry (with Industrial Placement)
- Year 4 of F110 MChem Chemistry (with Industrial Placement)
- Year 4 of F112 MChem Chemistry with Medicinal Chemistry with Industrial Placement
Year 5 of UCHA-F107 Undergraduate Master of Chemistry (with Intercalated Year)
UCHA-F109 Undergraduate Master of Chemistry (with International Placement)
- Year 4 of F109 MChem Chemistry (with International Placement)
- Year 4 of F111 MChem Chemistry with Medicinal Chemistry (with International Placement)
UCHA-4M Undergraduate Master of Chemistry Variants
- Year 4 of F105 Chemistry
- Year 4 of F110 MChem Chemistry (with Industrial Placement)
- Year 4 of F109 MChem Chemistry (with International Placement)
- Year 4 of F126 MChem Chemistry with Med Chem (with Prof Exp)
- Year 4 of F125 MChem Chemistry with Medicinal Chemistry
- Year 4 of F106 MChem Chemistry with Professional Experience
Year 5 of UCHA-F127 Undergraduate Master of Chemistry with Medicinal Chemistry(with Intercalated Year)