I just want to append to this thread some additional comments for any future reader:
1) As Anselm suggested, the discrepancy between my computed RESP charges and the standard ff14sb charges was almost entirely due to the dependence on confirmation. To account for this aspect, I performed a multi-conformational RESP fit for 1652 conformers of Tyr (capped by ACE and NME). The conformers were taken from the particular Tyr in the protein system I plan on mutating. I figured conformers fairly close to the ones sued in the original charge derivation may be among the distribution of states sampled from the MD with those charges. The charges I now obtain all fall within 0.08 of the original charges, which is significantly better than before.
2) I found helpful the discussion of charge derivation in Robalo et al., "The Multiple Origins of the Hydrophobicity of Fluorinated Apolar Amino Acids” Chem, 2017, 3, 881–897.
Best,
Matthew
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Received on Sat Jan 01 2022 - 10:00:02 PST
