Hello Tarsis,
Cysteine has not been parametrized for constant pH and redox, so you would need to do it yourself. The Amber manual has some instructions for that. You would need to know pKas and standard redox potentials in a reference environment. However, long story short, cysteine pKa predictions are not good; I believe changes in the constant pH methodology are necessary to address this issue.
All the best,
Vinícius Wilian D. Cruzeiro, PhD
Scientist II, Computational Chemistry
Architect Therapeutics
Twitter: .vwcruzeiro
On Oct 27, 2023, at 11:14 PM, Ferreira, Tarsis G via AMBER <amber.ambermd.org> wrote:
Hi,
I would like to run constant pH and Redox Potential to analyze changes in the redox potential of a cysteine pair. I checked titratable_residues.py and CYS does not have an electrostatic correction. Can someone confirm if I could proceed by just adjusting eleccnt=0 and typ="phredox"
# Cysteine
refene1 = _ReferenceEnergy(igb2=77.4666763, igb5=76.2588331, igb8=71.5804519)
refene1.solvent_energies(igb2=77.6041407, igb5=76.2827217)
refene1.dielc2_energies(igb2=38.090523, igb5=37.454637)
refene1.dielc2.solvent_energies(igb2=38.489170)
# Copying the reference energy to be printted on the old CPIN format
refene1_old = _ReferenceEnergy(igb2=77.4666763, igb5=76.2588331, igb8=71.5804519)
refene1_old.solvent_energies(igb2=77.6041407, igb5=76.2827217)
refene1_old.dielc2_energies(igb2=38.090523, igb5=37.454637)
refene1_old.dielc2.solvent_energies(igb2=38.489170)
refene1_old.set_pKa(8.5, deprotonated=False)
refene2 = _ReferenceEnergy(igb2=0, igb5=0, igb8=0)
refene2.solvent_energies(igb1=0, igb2=0, igb5=0, igb7=0, igb8=0)
refene2.dielc2_energies(igb2=0, igb5=0, igb8=0)
refene2.dielc2.solvent_energies(igb1=0, igb2=0, igb5=0, igb7=0, igb8=0)
CYS = TitratableResidue('CYS', ['N', 'H', 'CA', 'HA', 'CB', 'HB2', 'HB3', 'SG',
'HG', 'C', 'O'], pka=8.5, typ="phredox")
CYS.add_state(protcnt=1, eleccnt=0, refene=refene1, refene_old=refene1_old, pka_corr=8.5, # protonated
charges=[-0.4157, 0.2719, 0.0213, 0.1124, -0.1231, 0.1112, 0.1112,
-0.3119, 0.1933, 0.5973, -0.5679])
CYS.add_state(protcnt=0, eleccnt=0, refene=refene2, refene_old=refene2, pka_corr=0.0, # deprotonated
charges=[-0.4157, 0.2719, 0.0213, 0.1124, -0.3593, 0.1122, 0.1122,
-0.8844, 0.0, 0.5973, -0.5679])
CYS.check()
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Received on Sat Oct 28 2023 - 11:00:02 PDT
