Vibrational energy transfer (VET) is emerging as key mechanism for protein functions, possibly playing an important role for energy dissipation, allosteric regulation, and enzyme catalysis. A deep understanding of VET is required to elucidate its role in such processes. Ultrafast VIS‐pump/IR‐probe spectroscopy can detect pathways of VET in proteins. However, the requirement of having a VET donor and a VET sensor installed simultaneously limits the possible target proteins and sites; to increase their number we compare six IR labels regarding their utility as VET sensors. We compare these labels in terms of their FTIR, and VET signature in VET donor‐sensor dipeptides in different solvents. Furthermore, we incorporated four of these labels in PDZ3 to assess their capabilities in more complex systems. Our results show that different IR labels can be used interchangeably, allowing for free choice of the right label depending on the system under investigation and the methods available.

Vibrational energy transfer in proteins has been related to enzyme catalysis, energy dissipation, and allosteric communication. In their Research Article (e202200648), Jens Bredenbeck et al. establish a broad palette of vibrational energy sensors. A variety of functionalities are used to cover chemical and steric diversity. Their comparable responsivity allows for choosing a suitable non‐canonical amino acid for each site, as exemplified for a showcase allosteric protein.

Schwingungsenergietransfer in Proteinen wird mit der Katalyse von Enzymen, der Energiedissipation und der allosterischen Kommunikation in Verbindung gebracht. In ihrem Forschungsartikel (e202200648) stellen Jens Bredenbeck und Mitarbeiter eine breite Palette von Schwingungsenergiesensoren vor. Eine Vielzahl von Funktionalitäten deckt die chemische und sterische Vielfalt ab. Ihre vergleichbare Responsivität ermöglicht es, für jede Position eine geeignete nicht‐kanonische Aminosäure zu wählen, wie am Beispiel eines allosterischen Proteins gezeigt wird.

Vibrational energy transfer (VET) is emerging as key mechanism for protein functions, possibly playing an important role for energy dissipation, allosteric regulation, and enzyme catalysis. A deep understanding of VET is required to elucidate its role in such processes. Ultrafast VIS‐pump/IR‐probe spectroscopy can detect pathways of VET in proteins. However, the requirement of having a VET donor and a VET sensor installed simultaneously limits the possible target proteins and sites; to increase their number we compare six IR labels regarding their utility as VET sensors. We compare these labels in terms of their FTIR, and VET signature in VET donor‐sensor dipeptides in different solvents. Furthermore, we incorporated four of these labels in PDZ3 to assess their capabilities in more complex systems. Our results show that different IR labels can be used interchangeably, allowing for free choice of the right label depending on the system under investigation and the methods available.