Quantum dynamics of excited state proton transfer in green fluorescent protein¶

Authors: Susannah Bourne-Worster, Graham A. Worth

Takeaways:

Using direct quantum dynamics, we have confirmed that excited state proton transfer along the proton wire in GFP proceeds in a concerted, asynchronous fashion, led by abstraction of a proton from Ser205 by the Glu222 anion.
There is a significant activation barrier to deprotonating Ser205, and tunneling through this barrier plays a critical role in allowing the proton transfer to proceed at a reasonable rate.
Deprotonating Ser205 makes subsequent proton transfers along the wire energetically more favorable—possibly even barrierless.

Abstract¶

Photoexcitation of green fluorescent protein (GFP) triggers long-range proton transfer along a “wire” of neighboring protein residues, which, in turn, activates its characteristic green fluorescence. The GFP proton wire is one of the simplest, most well-characterized models of biological proton transfer but remains challenging to simulate due to the sensitivity of its energetics to the surrounding protein conformation and the possibility of non-classical behavior associated with the movement of lightweight protons. Using a direct dynamics variational multiconfigurational Gaussian wavepacket method to provide a fully quantum description of both electrons and nuclei, we explore the mechanism of excited state proton transfer in a high-dimensional model of the GFP chromophore cluster over the first two picoseconds following excitation. During our simulation, we observe the sequential starts of two of the three proton transfers along the wire, confirming the predictions of previous studies that the overall process starts from the end of the wire furthest from the fluorescent chromophore and proceeds in a concerted but asynchronous manner. Furthermore, by comparing the full quantum dynamics to a set of classical trajectories, we provide unambiguous evidence that tunneling plays a critical role in facilitating the leading proton transfer.

Introduction¶

The interpretation of the biphasic ESPT kinetics is still under debate.

The corresponding GSPT process has been confirmed experimentally2,8 and theoretically13,14 to proceed via a concerted, asynchronous mechanism where the initial, rate-limiting step is proton transfer from Ser205 to Glu222.