Protein Dynamics Flashcards
(28 cards)
What does a protein look like?
Generally globular
Structure determines _
Function
Flexible proteins are difficult to crystalise. How might you fix this?
Sometimes more flexible domains are removed
What can normal mode calculation be used for?
To show the movement
What are the pre-simulation decisions?
- Which theory level to use
- Which software to use
- Which is the most appropriate force field
What are the levels of theory?
Molecular mechanics (Newtonian physics – A-Level mechanics stuff)
ab initio. (Quantum mechanics – better for smaller things like electrons)
How do you do a molecular dynamics simulation?
Start with protein in a vacuum in a defined box.
Add solvent molecules.
Then minimise – system finds thermodynamic structural minimum (“true structure”)
Then equilibrated until it is at the thermodynamic starting point and run.
What do molecular dynamics simulations tell us?
They give lots of data about the movements of each atom.
What intramolecular interactions should you be aware of?
- Cysteine allows for S-S covalent bonds (disulphide bridges)
- Ionic interactions like salt bridges
- Hydrogen bonds
- Van der Waals
Why are interactions with water important?
Interior of proteins is usually hydrophobic
Why are π systems important?
π systems like to stack on top of each other which is stabilising
What determines the rate of protein folding?
Thermodynamics - the Eyring Equation
Levinthal’s paradox
Proteins fold faster than expected
What is Anfinsen’s principle?
No single barrier between folded and unfolded pathways - an number of barriers
Many discrete thermodynamic minima along the way.
So sometimes proteins misfold and get stuck in wells
What factors determine ΔG° ?
o Hydrophobic effect
o Hydrogen bonds
o Electrostatic interactions
o Conformational entropy – how flexible the protein is
Unfolded protein has _ conformational entropy
High
Folded protein has _ conformational entropy
Low
Is the ΔGfolding usually big or small?
Small,
Proteins are only stabilised by a few hydrogen bonds, allows for fast turnover
What contributes to favourable ΔHfolding?
H-bonds
Salt bridges
Van der Waals
What contributes to favourable ΔSfolding?
Hydrophobic effect which involves excluding water and increasing the entropy of water
What makes ΔSfolding unfavourable?
Increased structuring of polypeptide chain
Network of structured protein on the outside of the protein
The more flexible the protein is, the more _ the system
Favourable
What doe the elliptical phase diagram tell us?
How pressure and temperature alter the structure in different ways
What is compressibility?
This measures how much a protein’s volume changes under pressure.
A higher compressibility indicates a more flexible structure, allowing for a wider range of conformations and thus, reaction rates.
