The aim of this module is to discuss the application of basic physical chemistry concepts for describing protein structure and dynamics and to show how advanced physical chemistry methods are used for investigating these important aspects of proteins.

(LO1) Ability to discuss the importance of protein structure and dynamics for understanding biological processes.

(LO2) Ability to describe the experimental methods that are used to study structure, folding and fast dynamics of proteins.

(LO3) Ability to discuss the physical chemistry principles underlying these methods and apply the basic equations needed for the analysis of such data.

(LO4) Ability to describe and discuss some of the theoretical methods that are used to predict protein structure and and model protein folding/dynamics.

(LO5) Ability to analyse PDB-structure files and create meaningful graphical representations from these files.

(S1) Information skills - Information accessing:[Locating relevant information] [Identifying and evaluating information sources]

(S2) Critical thinking and problem solving - Critical analysis

(S3) Numeracy/computational skills - Problem solving

This module consists of 14 50-minute lectures covering theoretical aspects and experimental approaches to protein structure, folding and dynamics. The lectures will be supported by 2 tutorials, in which problem questions on the lecture material (which students will have been given in advance) will be discussed in detail, one literature seminar, in which a relevant primary research paper will be discussed, and one workshop, in which the use of a molecular visualisation program for displaying, animating and analysing protein structures is demonstrated.

This lecture course deals with topics at the interface between physical chemistry and biology, which is of increasing importance as physical chemical methods and ideas are being applied to understanding biological processes. The course is split into three sections. Section A deals with protein structure determination, Section B discusses protein folding, and Section C briefly outlines the importance of fast protein dynamics.

A Protein Structure
• Protein structure classification: Primary, secondary, tertiary, quaternary
• Ramachandran plot
• Secondary structural elements: alpha-helix, beta-sheets, turns, others
• Importance of 3D structure for function
• Methods for protein structure determination: diffraction methods, NMR, CD, FTIR/Raman
• Protein data bank
• Physical chemistry background: protein crystallisation, diffraction of X-rays electrons and neutrons, 2D-NMR, dipole interactions, elect ronic and vibrational spectroscopies
• Methods of protein structure prediction: Molecular Dynamics calculations, Zimm-Bragg statistical mechanics model of helix formation

B Protein Folding
• Forces relevant for protein folding
• Hydrophobic interaction and its thermodynamic consequence: cold- and heat denaturation
• DSC (Differential Scanning Calorimetry) for determination of thermodynamic parameters of folding
• Levinthal paradoxon
• Basic models of protein folding
• Observing the folding process - initialisation methods: rapid mixing, photochemical methods, temperature and pH jumps
• Observing the folding process - detection: Fluorescence (Förster transfer, FRET, spectral shifts), UV/vis-absorbance, CD, FTIR/Raman, NMR, H/D-exchange
• Folding kinetics analysis: Chevron plot, Phi-value analysis

C Protein Dynamics
• Examples and timescales of protein dyna mics - femtoseconds to minutes
• Examples of methods for investigating fast protein dynamics: H/D-exchange and Molecular Dynamics