fgrunewald
commented
1 year ago @KasperBuskPedersen we have not explore a mean-field histidine. Of course a constant pH approach would really be the better solution, which is something we work on. However, I'm not sure given the parametrisation strategy of Martini, that a mean-field HIS residue would yield an improved accuracy over chosen the more prevalent form. Do you have any specific data or test-case?
FYI I will convert this issue to a discussion, given that it concerns the protein model on a more general level rather than a code issue.
Hi @fgrunewald and martinize2 developers (even though this issue would probably be more appropriate in a protein development group)
Histidine pka can be significantly shifted inside proteins, often in the ranges of 5-7, sometimes even higher, meaning that at pH 7 one histidine have significant subpopulations of both the neutral tautomers and the protonated charged histidine.
In a coarse-grained model it would therefore make good sense to have a mean field topology (in lack of a better word), halfway between say HIE and HIP. Something like:
P2 HIM BB 0.0 TC4 HIM SC1 0.0 TN6d HIM SC2 0.25 TN6d HIM SC3 0.25
Is this something you have explored? The issue is ofc that the non-integer charge should be counteracted by some small number of modified ions e.g. NAX charge=0.9
Best regards Kasper