CH412-15 Advanced Biophysical Chemistry

Department: Chemistry
Level: Undergraduate Level 4
Module leader: Rebecca Notman
Credit value: 15
Module duration: 20 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 four Parts, of which two or four may be chosen for 15 CATS or 30 CATS respectively. These are:

Part 1: Electron Paramagnetic Resonance (EPR)
This part module introduces the EPR spectroscopy technique. The similarities and differences of EPR vs NMR spectroscopy will be discussed, including relative sensitivity, specificity and selectivity, motional timescales, pulsed vs continuous wave techniques and underpinning principles. The information content of EPR spectra will be considered, some modern pulsed EPR techniques introduced and common biological applications discussed.

Part 2: Dynamics by NMR
This part module introduces NMR as a technique to study molecular motions and dynamic processes. State-of-the-art methods in solution and solid state will be surveyed. Their theoretical underpinnings and practical experimental implications will be discussed. Module will emphasise applications to study motions in biomolecules.

Part 3: 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 4: 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: Electron Paramagnetic Resonance

Comparing EPR and NMR. Electron in a magnetic field; Spin polarization; Energies of electron vs proton. Sensitivity of EPR vs NMR; Fermi’s golden rule – transition probabilities and population difference; Dynamic Nuclear Polarization - using EPR to enhance NMR sensitivity.
Nuclei in EPR. g-value vs chemical shift. Paramagnetic vs spin resonance - Quenching of orbital angular momentum; Experimental aspects of EPR; Origin of hyperfine coupling (dipole-dipole, fermi-contact, polarization); Energy levels of strong and weakly coupled systems; Hyperfine coupling patterns; The McConnell equation and Huckel theory.
Nitroxide EPR. Hyperfine and g anisotropy; Dynamic effects and linewidths in EPR; Multifrequency EPR and g anisotropy; Nitroxide spin labelling; Spin trapping.
Introduction to Pulsed EPR. Bandwidth limitations and deadtime; FIDs and spin echoes; Relaxation times in EPR; Distance measurements by Double Electron Electron Resonance (DEER).
Hyperfine spectroscopy. CW & pulsed ENDOR; ESEEM and HYSCORE.
Special topics in EPR. High spin systems – allowed and forbidden transitions; Other topics including one or more from: Transition metal EPR – copper spectra, high and low spin iron, Time-resolved EPR – radical pairs, applications to photosynthetic reaction centres and avian magnetoreception; Irradiation generation – DNA and excipient radicals.

Part 2: Dynamics by NMR

Introduction to protein dynamics. Protein energy landscapes. Review of NMR interactions.
Motional averaging of anisotropic NMR interactions. Order parameters. Residual dipolar couplings. Fundamental differences between solution and solid-state NMR.
Chemical exchange. Approaches to study chemical exchange in fast, intermediate and slow exchange regime. Relaxation dispersion. Invisible states.
NMR relaxation and molecular motions. Basics of semi-classical relaxation theory. Correlation function. Spectral density. Model free formalism. Auto-relaxation, cross-relaxation and cross-correlated relaxation. Nuclear Overhauser Effect (NOE). Transverse Relaxation-Optimised Spectroscopy (TROSY).

Part 3: 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 4: 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: Electron Paramagnetic Resonance

P. Atkins and J De Paula, Atkins’ Physical Chemistry (9th ed.), OUP (2009).
G.R Eaton, S.S. Eaton, D.P. Barr and R.T. Weber, Quantitative EPR, Springer (2010).
A. Schweiger and G. Jeschke, Principles of Pulsed Electron Paramagnetic Resonance, OUP (2001).
V. Chechik, E. Carter and D. Murphy, Electron Paramagnetic Resonance, OUP (due for publication 23rd June 2016).

Part 2: Dynamics by NMR

M.H. Levitt, Spin Dynamics.
G.S. Rule, Fundamentals of Protein NMR Spectroscopy.

Part 3: Biomolecular simulation

A.R. Leach, Molecular Modelling: principles and applications, Longman (1996).
M.A. Allen and D.J. Tildesley, Computer Simulation of Liquds, Clarendon Press (1989).
A selection of papers from the recent research literature, that may change from year to year, will also be provided.

Part 4: 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 ScientistsCavanagh, 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.

Interdisciplinary

e.g. co-taught with another department or with an industry perspective, bridges two or more disciplinary concepts, ideas, etc

Subject specific skills

Problem solving
Written communication
Oral communication

Transferable skills

Problem solving
Written communication
Oral communication

Teaching split

Provider	Weighting
Chemistry	75%
Physics	25%

Study time

Type	Required
Lectures	12 sessions of 1 hour (8%)
Practical classes	5 sessions of 1 hour (3%)
Private study	133 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 D1

	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
Online 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)