Stretching vibrational frequencies and pK a differences in H-bond networks of protein environments.

The experimentally measured stretching vibrational frequencies of O-D [ν _O-D (donor)] and C=O [ν _C=O (donor)] H-bond donor groups can provide valuable information about the H-bonds in proteins. Here, using a quantum mechanical/molecular mechanical approach, the relationship between these vibrational frequencies and the difference in pK _a values between H-bond donor and acceptor groups [ΔpK _a (donor … acceptor)] in bacteriorhodopsin and photoactive yellow protein environments was investigated. The results show that ν _O-D (donor) is correlated with ΔpK _a (donor … acceptor), regardless of the specific protein environment. ν _C=O (donor) is also correlated with ΔpK _a (donor … acceptor), although the correlation is weak because the C=O bond does not have a proton. Importantly, the shifts in ν _O-D (donor) and ν _C=O (donor) are not caused by changes in pK _a (donor) alone, but rather by changes in ΔpK _a (donor … acceptor). Specifically, a decrease in ΔpK _a (donor … acceptor) can lead to proton release from the H-bond donor group toward the acceptor group, resulting in shifts in the vibrational frequencies of the protein environment. These findings suggest that changes in the stretching vibrational frequencies, in particular ν _O-D (donor), can be used to monitor proton transfer in protein environments.
Competing Interests: Declaration of interests The authors declare no competing interests.
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