LK peptide side chain dynamics at interfaces are independent of secondary structure

Abstract

Protein side chain dynamics are critical for specific protein binding to surfaces and protein-driven surface manipulation. At the same time, it is highly challenging to probe side chain motions specifically at interfaces. One important open question is the degree to which the motions of side chains are dictated by local protein folding or by interactions with the surface. Here, we present a real-time measurement of the orientational dynamics of leucine side chains within leucine-lysine (LK) model peptides at the water-air interface, with three representative peptide folds: α-helix, 3-helix and β-strand. The results, modeled and supported by molecular dynamics simulations, show that the different peptide folds exhibit remarkably similar sub-picosecond orientational side chain dynamics at the air/water interface. This demonstrates that the side chain motional dynamics is decoupled from the local secondary structure.

Mirror-image antiparallel β-sheets organize water molecules into superstructures of opposite chirality

“…Indeed, the LK 7 β peptide and its variants in native (L-) form have been commonly used as a model system in surface studies. (2,(8)(9)(10)(11)(12)(15)(16)(17) We obtain the phase-resolved chiral SFG vibrational spectra of (L-) and (D-) LK 7 β in the spectral regions of the O-H/N-H stretching at ∼3,200 cm −1 using H 2 O as solvent and the O-D/N-D stretching at ∼2,400 cm −1 using D 2 O. We also perform the experiments using H 2 18 O and D 2 18 O.…”

Measuring the Multiscale Dynamics, Structure, and Function of Biomolecules at Interfaces

“…The relationship between structure, dynamics, and function is a cornerstone of biophysical studies, but lessons gained from bulk characterization tools are not always applicable to interfaces. For example, while solution NMR studies have led to an understanding that protein side chain dynamics are dependent on their local chemical environment, model peptides with distinct secondary structures (α-helix, 3 10 -helix, and β-sheet) at the air–D 2 O interface show that leucine residues’ methyl side chains undergo reorientational dynamics that are independent of their local structure . Moreover, the importance of the immediate chemical environment is highlighted by the observation that H 2 O bending modes can couple resonantly to the amide I vibrations of proteins and provide an effective relaxation pathway, while that is not the case for D 2 O .…”

“…Recent examples highlight the dominant role of heterogeneity, environment-dependent conformational transformations, and individual as well as collective dynamics. Images reproduced with permission from refs , , and (clockwise from top). Copyrights: 2018 American Chemical Society, 2019 American Chemical Society, and 2017 The Royal Society of Chemistry.…”

“…To probe the fast end of the wide range in structural and functional dynamics displayed by large macromolecular systems, one finds primarily ultrafast spectroscopy tools that build upon decades of technique development across the electromagnetic spectrum. Most notably, time-resolved sum frequency generation (SFG), two-dimensional SFG, and two-dimensional infrared (2D-IR) spectroscopies provide exquisite sensitivity to vibrational modes with ultrafast temporal resolution. , These tools not only can resolve structural features but also can identify vibrational relaxation and energy transfer , and follow the dynamic reorientation of molecular subunits. , While it is possible to achieve surface sensitivity with odd-order spectroscopies, − probes of interfaces have typically been associated with even-order nonlinear spectroscopies whose signal arises specifically from an interface as a result of its broken symmetry. Recently, a broadly applicable way to impart surface specificity to odd-order nonlinear spectroscopies by using polarization was proposed by Zanni and co-workers, opening new avenues to study dynamics at interfaces in the ultrafast regime …”

Direct Evidence for Aligned Binding of Cellulase Enzymes to Cellulose Surfaces

“…Surface-specific sum frequency generation (SFG) spectroscopy and atomistic simulations have recently been combined into a versatile tool to determine protein structure at interfaces. − We use this strategy here to probe the equilibrium structure and binding orientation of the CBM-P cellulase peptide mimic on cellulose. As a model cellulose surface, we deposited highly oriented cellulose fibers on glass substrates .…”