Hello NAMD Community,
I am simulating Protein with two Zinc ions in the active pocket. Two types of parameter files are introduced in conf.file (par_all36_prot.prm and par_all22_prot_metals.inp). Both the Zinc ions moved slightly in the pocket as a result their actual trigonal interaction symmetry with HIS and SER is disappeared. I am interested to mimic pH 7.5. Please suggest me for, i. How Should I keep my Zinc in a stable interactional state. ii. What could be the best protonation state of HIS for pH 7.5 and iii. What other things I should take care of for pH 7.5. My goal is to study Zinc behavior after 20ns rather protein conformation.
Thanks to all the NAMD experts.
An excellent question. Zinc is such a nutrient that expesses its suboptimum supply in soil under bother acidic as well as alkaline soil conditions...but pH is not so easy to main around 7.5...
pKa of the imidazole sidechain of HIS is about 6.0. For pH 7.5, it should be deprotonated. The deprotonated HIS may also helpful in stabilizing the Zinc ion. If it still doesn't work, I would suggest you to run a simulation with constrains on the distance between the sidechain of HIS and Zn and between the sidechain of SER and Zn to maintain the trigonal interaction for a while. Then release the constrains after the system become stable. For simulations at a specific pH, e.g. 7.5, run a pH prediction of all the residues before building the model is necessary. There are some software can help you to do that, for example H++, propka. But you still have to inspect the protonation state of each residue carefully, especially, those in the active site.
Thanks Peng for a detail answer. I have applied the harmonic restraints on both Zn atoms and it looks better somehow in the pocket.
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