[gmx-users] Predict Physical Properties of Novel Proteins

Justin Lemkul jalemkul at vt.edu
Sun Apr 22 22:09:51 CEST 2018

On 4/22/18 3:53 PM, Academic Research wrote:
>> Hello Everyone,
> I am computationally designing proteins, and I would like to ask if it 
> is possible to simulate the physical properties of these proteins on 
> gromacs in an attempt to filter the bad proteins from the good 
> proteins, which I would then use to spend money/energy on 
> expressing/purifying etc...
> I am not looking for folding simulations since I already have another 
> system for that.
> First of all, can molecular dynamics be used to predict the physical 
> properties of proteins? If not accurately, then at least allow me to 
> differentiate between horrible proteins (very low stability) from 
> proteins that are more likely to be stable in solution?
> Second, other than Rg, RMSD, aggregation in solution, and 
> thermostability, what other useful physical properties can gromacs 
> measure out of a simulation? crystilisability?

Rg and RMSD can give an initial impression of stability. You won't be 
able to measure aggregation in solution unless you carry out extensive 
simulations of many proteins in a unit cell (and probably enhanced 
sampling, on top of that) - that's an entire Ph.D. project on its own. 
Thermostability again requires lots of simulations at different 
temperatures. There is no way I know of to determine "crystallizability" 
from an MD simulation.

> I have successfully gone through the Lysozyme in Water tutorial 
> prepared by the Bevan Lab. Being new to gromacs, and simulating 
> totally novel proteins, would the parameters in that tutorial be a 
> standard in simulating water soluble globular proteins? would they 
> need just some tweaking? or should I start the parameters from scratch?

Don't consider any tutorial "standard." You're looking at something very 
complex. Whether or not the OPLS-AA force field is suitable is an open 
question, one that you need to investigate thoroughly. If you change the 
force field, you need to change the nonbonded settings accordingly. The 
time frame should also be several orders of magnitude longer, and you'll 
need to also consider ionic strength of the solution. Neutralizing 
counterions is a bit artificial, but salt screening effects can be quite 
significant, so it depends entirely upon what you want to model and what 
experimental conditions have been/will be used.



Justin A. Lemkul, Ph.D.
Assistant Professor
Virginia Tech Department of Biochemistry

303 Engel Hall
340 West Campus Dr.
Blacksburg, VA 24061

jalemkul at vt.edu | (540) 231-3129


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