I would like to know if there is an established procedure for dealing with structures having a high net-charge. I am not a chem, but I understand that this will mess with the simulation. I am aware that counter-ions should be added to stabilize the system. Therefore, I have the following questions. Any relevant resources or keywords to search would be really helpful for me.
What is an acceptable non-zero net-charge? How could we estimate this? Does it have to do with the hydrophobic to hydrophilic residues ratio?
Do we have to look for the protonation states in the protein’s isoelectric point? Will that pH be realistic in vivo?
There is a worse scenario of having a non-integer net-charge. Any pointers on this? Is there any guide available how to tackle this?
Thank you in advance.