Examiners: Hünenberger, Riniker
Comments: 15min with each examiner, an assistant is present and takes notes throughout. Relaxed, friendly atmosphere, but quite fast-paced; Hünenberger provides hints when needed, don’t know about Riniker (didn’t come up). Exam conducted via Zoom due to COVID pandemic situation.
Hünenberger
Why do we not exclusively simulate at the QM level?
(unfavourable scaling)
How dow QM methods scale?
(n^3 or worse)
What can’t we do with MD?
(covalent chemistry, spectroscopy etc.)
How do we do MD?
(integrate Newton’s equations of motion)
Can you write down the Hamiltonian of our system?
( H = K(q,p) + V(q) )
Can you write down the Hamiltonian equations of motion?
( *write them down* )
Do you know which one corresponds to F = ma?
(the one with (del H/ del q) )
What does the force-field term for electrostatics look like generally?
(*write down*)
What about van der Waals?
(*write down*)
Where do we get those C6/C12 from?
(parametrise against rare gases, draw a little sketch of curve, explain ε, σ etc.)
And if you had two different atom types?
(*write down combination rule for C6/C12*, mention some alternatives)
What ensemble do we sample with plain MD?
(NVE)
And with MC?
(NVT)
Can you explain how Monte Carlo works?
(*do it*)
Do you remember what the move acceptance criterion is?
(*write it down*, mention it’s meant to keep the ensemble Boltzmann)
Could you preferentially pick moves along the direction of current force to enhance sampling?
(Technically no, the choice of a candidate next state has to be unbiased. He mentions that biased MC exists, but you have to correct for the bias.)
Do you remember the definition of the instantaneous temperature?
(*write down*)
A system of 100 diatomic molecules with bond constraints has how many degrees of freedom?
(200*3 - 100 = 500)
What about the instantaneous pressure?
(*write down*)
And the virial?
(*write down*)
How do thermostating and barostating work conceptually?
(*scale the things*)
Why would someone want to supply the compressibility to …?
(My memory is a bit fuzzy here, it was either a thermostat or a barostat. He wanted me to connect it to the instantaneous pressure expression somehow, but I didn’t quite get it in the moment. Something about controlling temperature and pressure simultaneously. I couldn’t answer the question and he said “don’t worry”, and we moved on to the second part of the exam)
Riniker
You talked about MC. How does Temperature Replica Exchange work?
(*explain*)
What is the exchange acceptance criterion?
(*write down*)
How does Umbrella Sampling work?
(*explain*)
How would you do the reweighing?
(*write down formula*)
What about accelerated MD, how is that different?
(*explain, write down formula, draw a little picture*)
How would you get a conformational free energy difference from Umbrella Sampling?
(*formula*, explain what the binary assignment functions do, how they could be defined in terms of RMSD)
Would these assignment functions change if your states of interest or the system were to change?
(*Yes. Not necessarily the functional form, but yes.*)
How would you go about getting a relative binding free energy of two ligands to a protein?
(*draw the thermodynamic cycle, say which transitions you simulate*)