MD simulation at low pH

GROMACS version: 18.1
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I am Gulshan Kumar from Mumbai, India. I want to simulate a viral enevelop protein at low pH (6 and 4). I did simulation at normal pH. Please suggest changes required in the protocol. If any good refernce available (for begineers) regarding this, please suggest.

You can assign different protonation states to titratable residues when running pdb2gmx using the relevant command-line flags. I would not call that simulating at a different pH, because protonation states are not dynamic like they are in a buffered solution at a given pH, but it is a reasonable model of simulating something in its dominant form at a given pH.

Thank You sir for your response. It will be good if you suggest any tool for prediction of protonation states of titratable residues in a protein.

H++, DelPhiPKa web server, reduce, etc. A simple Google search turns up lots of options.

Thanks a lot

Hi @Gulshan , what server/software do you use to change the pH of the protein (.pdb) ? I tried using propka and yasara but it caused an error at the beginning of the topology creation

I used H++ and pdb2pqr servers for identifying protonation states of the residues. I have taken pdb files and made topology using CHARM GUI server but not simulated yet. So I can’t tell about errors in subsequent steps.

Hi @jalemkul,

I wonder when you said

protonation states are not dynamic like they are in a buffered solution at a given pH

do you mean the pH will be the same during the whole simulation? Sorry I’m a beginner in this area and I guess I lack certain chemical knowledge to understand it. Would really appreciate it if you can offer any additional info.

See my other answer to your other post. But to answer the question, no this does not mean pH is constant, because in most cases there is no concept of pH, because there are no free H+ (or really H3O+). So pH is undefined. The protonation states of titratable groups are fixed.

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It makes sense. Thank you!