QM/MM study of proton transport process in [FeFe] hydrogenase enzyme

16 August 2021, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Di-iron hydrogenases are a class of enzymes that are capable of reducing protons to form molecular hydrogen with high efficiency. In addition to the catalytic site, these enzymes have evolved dedicated pathways to transport protons and electrons to the reaction center. Here, we present a detailed study of the most likely proton trans- fer pathway in such an enzyme using QM/MM molecular dynamics simulations. The protons are transported through a channel lined out from the protein exterior to the di-iron active site, by a series of hydrogen-bonded, weakly acidic or basic, amino-acids and two incorporated water molecules. Proton transport takes place via a ”hole” mech- anism, rather than an excess proton mechanism, the free energy landscape of which is remarkably flat, with a highest transition state barrier of only 5 kcal/mol. These results confirm our previous assumptions that proton transport is not rate limiting in the H2 formation activity and that cystene C299 may be considered protonated at physiological pH conditions. Detailed understanding of this proton transport may aid in the ongoing attempts to design artificial bio-mimetic hydrogenases for hydrogen fuel production.


[FeFe] hydrogenase
Proton Transfer
Free energy calculations
QM/MM simulations


Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.