Secondary structure effects on internal proton transfer in poly-peptides.

M Bouakil,F Chirot,M Girod,P Dugourd,L Macaleese

doi:10.1063/4.0000003

Abstract

A pump–probe approach was designed to determine the internal proton transfer (PT) rate in a series of poly-peptide radical cations containing both histidine and tryptophan. The proton transfer is driven by the gas-phase basicity difference between residues. The fragmentation scheme indicates that the gas-phase basicity of histidine is lower than that of radical tryptophan so that histidine is always pulling the proton away from tryptophan. However, the proton transfer requires the two basic sites to be in close proximity, which is rate limited by the peptide conformational dynamics. PT rate measurements were used to probe and explore the peptide conformational dynamics in several poly-glycines/prolines/alanines. For small and unstructured peptides, the PT rate decreases with the size, as expected from a statistical point of view in a flat conformational space. Conversely, if structured conformations are accessible, the structural flexibility of the peptide is decreased. This slows down the occurrence of conformations favorable to proton transfer. A dramatic decrease in the PT rates was observed for peptides HAnW, when n changes from 5 to 6. This is attributed to the onset of a stable helix for n = 6. No such discontinuity is observed for poly-glycines or poly-prolines. In HAnW, the gas-phase basicity and helix propensity compete for the position of the charge. Interestingly, in this competition between PT and helix formation in HA6W, the energy gain associated with helix formation is large enough to slow down the PT beyond experimental time but does not ultimately prevail over the proton preference for histidine.

Highlights

Complex molecular systems, such as biomolecules or molecular machines, derive a large part of their remarkable properties from their ability to self-organize and adapt their structure to their environment
We have recently shown that, in the model peptide HG3W, internal proton transfer and conformational dynamics are deeply connected: conformational dynamics controls the proximity between the basic sites, which limits the kinetics of proton transfer in the peptide.[18]
The proton transfer was earlier found to be rate limited by the peptide conformational dynamics, and the rationale was to use it as a signature for the very same peptide conformational dynamics

Summary

Introduction

Complex molecular systems, such as biomolecules or molecular machines, derive a large part of their remarkable properties from their ability to self-organize and adapt their structure to their environment Conformational changes in such systems can be triggered by a variety of stimuli, including light absorption and temperature or pH changes. Despite its fundamental interest and the potential applications to design smart materials, the problem of understanding the interplay between the two mechanisms is difficult to tackle. It involves timescales spanning several orders of magnitude, in relation to the hierarchical structuration of the systems and the coupling between electronic and vibrational degrees of freedom

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