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.

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

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

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

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

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

Lecture -

Seminar -

Literature Seminar

Tutorial -

Laboratory Work -

VMD-workshop

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, 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 - detect ion:
  Fluorescence (Förster transfer, FRET, spectral shifts), UV/vis-absorbance, CD, FTIR/Raman, NMR, H/D-exchange
• Folding kinetics analysis: Chevron plot, Phi-value analysis

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