Protein Energetics Flashcards
What kind of bonds are Van der Waals?
How are they different to covalent bonds?
What do covalent bonds tell us?
Why do covalent/peptide bonds prefer staggered over eclipse conformation?
What is the steric effect?
What can eclipse torsions do?
Electrostatic, induction, dispersion
Much shorter range
Local sequence level
Angles are maximised so energy is minimised
Atoms in closer proximity increases the energy of the molecule (lower stability)
Induce forces
What are the attractive & repulsive forces in VDW?
What does the L-J model show with VDW (non-cov)?
Why are hydrogen bonds (non-cov) also modelled with the L-J potential?
How can you calculate covalent interactions?
What is the problem with calculating non-covalent interactions?
How can you overcome this?
Induced-dipole-induced-dipole (longer range) & electron-electron interaction (shorter range)
Sum of VDW radii at a certain distance between the atoms is the most favourable for producing the most energetically favourable interaction
Speeds up calculations & no loss of accuracy
From local sequence due to amino acids
Electrostatics & VDW have small effects over long distances (LJ) & calculation time is proportional to the number of atoms
Use a cut-off distance - fewer atoms
What are the 3 cutoffs and which is preferred? (modelling a force field)
On what law does molecular dynamics rely on?
What are the 4 steps to simulating a MD?
How can you improve the smoothness of the simulation?
How can you remove the need to calculate water energy in MD simulations?
Truncation, shift & switch
Switch - energy slowly goes towards 0 over time - isn’t a sudden shift in energy
Newton’s 2nd law F = ma
1. Choose short time frame & give atoms initial positions 2. Assign random velocity using Boltzmann distribution (related to temp) 3. Obtain forces from calculating energies from position & time Calculate acceleration of each atom
Verlet/Leapfrog algortihm - calculating coordinates of atom at each time step (t) and using this to update the velocities at t1/2 by using the acceleration from F = ma
3x3 bod grid - water moves with periodic boundaries because pressure is maintained
What are the 3 uses of MD simulations?
What can MD simulations not show? Why?
What is accounted for in MD models?
What are 3 examples of a hydrophobicity arbitrary scale?
Which forces have the largest effect in water?
Why is computational docking hard to simulate?
Why are MD simulations beneficial for computational docking models?
Protein dynamics
Energy minimisation
Docking (protein-protein/protein-substrate)
Protein folding - doesn’t account for the hydrophobic effect/entropy
Enthalpy - not entropy
Partioning methods (octanol & water)
Accessible surface area methods
Chromatography - different stationary & mobile phases
Hydrophobic effect, Hydrogen bonds
Can’t account for hydrophobicity, large search space (6D)
Accounts non-cov, flexibility of side chains & interactions with small molecules
