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 podcasts providing the material which normally would be presented in 14 50-minute lectures covering theoretical aspects and experimental approaches to protein structure, folding and dynamics.

The lectures will be supported by 2 synchronous tutorials/revision sessions (ideally face-to-face) in which quizzes and problem questions on the podcast material will be discussed in detail, which students will have to had to complete as small assignments while engaging with the material.

Students also will need to regularly engage in accompanying literature work, in which a relevant primary research paper will be dissected in parallel to the presentation of relevant podcast material

The students will use VMD, which is a protein structure and visualisation program. This will be taught in an (a)synchronous workshop, where (a)synchronous means that in principle students can work through this material in their own time, but several 2-hour Team meetings wil l be set up for students to drop in to get immediate help if they have any questions or have encountered any problems, and they will be advised to work through this material during one of those sessions. The workshop material itself will not be assessed. Following this workshop, students will be given tasks to complete independently, which will include downloading a particular protein structure, constructing graphical representations and the Ramachandran plot.

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, electron microscopy, CD, FTIR/Raman
• Protein data bank
• Physical chemistry background: protein crystallisation, diffraction of X-rays electrons and neutrons, 2D-NMR, dipol e interactions, electronic 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

C Protein Dynamics
• Examples and timescales of protein dyn amics - femtoseconds to minutes
• Examples of methods for investigating fast protein dynamics: Molecular Dynamics