Visualizing Cyclic Peptide Hydration at the Single-Molecule Level

Abstract

The role of water molecules in the selective transport of potassium ions across cell membranes is important. Experimental investigations of valinomycin–water interactions remain huge challenge due to the poor solubility of valinomycin in water. Herein, we removed this experimental obstacle by introducing gaseous water and valinomycin onto a Cu(111) surface to investigate the hydration of valinomycin. By combining scanning tunneling microscopy (STM) with density functional theory (DFT) calculations, we revealed that water could affect the adsorption structure of valinomycin. Hydrogen bond interactions occurred primarily at the carbonyl oxygen of valinomycin and resulted in the formation of valinomycin hydrates. The single-molecule perspective revealed in our investigation could provide new insight into the role of water on the conformation transition of valinomycin, which might provide a new molecular basis for the ion transport mechanism at the water/membrane interface.

Single-molecule insights into surface-mediated homochirality in hierarchical peptide assembly

“…In this case, it was defined as R-type configuration monomer (M R ) and simplified as a blue clockwise propeller. According to the corresponding relationships between molecular models, electron density images and STM images as our previous work presented, M L is seen as three lobes with a central protrusion, while M R appears as three lobes with a central cavity in the STM image 20 .

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“…1a , valinomycin is a cyclic dodecadepsipeptide, which consists of three repeated asymmetric chiral structural units, l -valine, d -hydroxyvaleric acid, d -valine, and l -lactic acid ( l -Val— d -Hyv— d -Val— l -Lac). Valinomycin is a nonplanar macrocyclic molecule having different chemical moieties at both sides of the annular backbone; therefore, it has two different landing faces to contact with surfaces 19 , 20 . STM observation (Fig.…”

Mass Spectrometry as a Preparative Tool for the Surface Science of Large Molecules

“…Nevertheless, the complexity of the interactions prevails and fundamental www.annualreviews.org • Mass Spectrometry as a Preparative Tool aspects such as folding or sequence-controlled assembly seem feasible in vacuum as well. In fact, surface-based studies in vacuum do not exclude the possibility of investigating the role of solvents at the molecular scale (137). Furthermore, the chemistry of ions at the surface, especially in collisions at hyperthermal energy, are worthy of investigation, both from chemical and morphological points of view (37,138).…”

Understanding and designing head‐to‐tail cyclic peptides

“…Several challenges are associated with using MD simulations to accurately and efficiently predict CP structures (Figure ). (1) Both experimental and computational studies have shown that solvent plays a significant role in the structure a CP adopts . Therefore, to accurately account for direct CP–solvent interactions, explicit solvent simulations are necessary.…”

“…Several computational methods have been used to design CPs, including virtual screening of CP libraries to identify CPs with high binding affinities for a given target, fragment‐based algorithms to predict CP structures, and molecular dynamics (MD) simulations to characterize the conformational ensembles of CPs . While virtual screening has been shown to be an effective method of surveying sequence space and identifying residues crucial for binding, it currently lacks the capability to accurately describe CP–solvent interactions, which have been shown to play a crucial role in the structures CPs adopt . Additionally, virtual screening methods are typically based on libraries of linear peptide and protein systems, and therefore may not be suitable to describe the conformations of CPs.…”