Through bonds or contacts? Mapping protein vibrational energy transfer using non-canonical amino acids

Erhan Deniz,Robert Kaml,Jan G Löffler,Gerhard Stock,Katharina B Eberl,Luis Valiño-Borau,Patrick M Durkin,Steffen Wolf,Jens Bredenbeck,Adnan Gulzar,Nediljko Budisa

doi:10.1038/s41467-021-23591-1

Abstract

Vibrational energy transfer (VET) is essential for protein function. It is responsible for efficient energy dissipation in reaction sites, and has been linked to pathways of allosteric communication. While it is understood that VET occurs via backbone as well as via non-covalent contacts, little is known about the competition of these two transport channels, which determines the VET pathways. To tackle this problem, we equipped the β-hairpin fold of a tryptophan zipper with pairs of non-canonical amino acids, one serving as a VET injector and one as a VET sensor in a femtosecond pump probe experiment. Accompanying extensive non-equilibrium molecular dynamics simulations combined with a master equation analysis unravel the VET pathways. Our joint experimental/computational endeavor reveals the efficiency of backbone vs. contact transport, showing that even if cutting short backbone stretches of only 3 to 4 amino acids in a protein, hydrogen bonds are the dominant VET pathway.

Highlights

Vibrational energy transfer (VET) is essential for protein function
Enzymes have been hypothesized to carry out reactions efficiently because the reaction coordinate is coupled to so-called reaction promoting vibrations, that coincide with efficient vibrational energy transfer pathways[5,6]
In the context of allosteric communication, an increasing number of theoretical studies is proposing distinct VET pathways between distant sites to coincide with pathways of allosteric signal propagation[2,7,8,9,10,11,12,13]

Summary

Introduction

Vibrational energy transfer (VET) is essential for protein function It is responsible for efficient energy dissipation in reaction sites, and has been linked to pathways of allosteric communication. While it is understood that VET occurs via backbone as well as via noncovalent contacts, little is known about the competition of these two transport channels, which determines the VET pathways To tackle this problem, we equipped the β-hairpin fold of a tryptophan zipper with pairs of non-canonical amino acids, one serving as a VET injector and one as a VET sensor in a femtosecond pump probe experiment. There are a number of experimental VET studies covering smaller peptides[14,15,16,17] and even proteins[18,19,20,21,22] with quite impressive time resolution, a systematic analysis of backbone versus contact efficiency for VET has not been achieved yet. Energy propagation is monitored by another spectroscopic transition, either vibrational[1,15,17,26,28] or electronic[29]

Methods

Results

Conclusion