Peptide conformation and oligomerization characteristics of surface-mediated assemblies revealed by molecular dynamics simulations and scanning tunneling microscopy

Abstract

The characteristics of peptide conformations in both solution and surface-bound states, using poly-glycine as a model structure, are analyzed by using molecular dynamics (MD) simulations. The clustering analysis revealed significant linearization effect on the peptide conformations as a result of adsorption to surface, accompanied by varied adsorption kinetics and energetics. Depending on the inter-peptide interaction characteristics, distinctively different surface-mediated oligomerization modalities, such as antiparallel conformations, can be identified in MD and confirmed by scanning tunneling microscopy (STM) analysis of the assembly structures. These observations are beneficial for obtaining molecular insights of assembling propensity relating to peptide-surface and peptide-peptide interactions.

Fig. 1. High resolution STM images of (A) G5 and (C) G6 co-assembled with 4Bpy. Tunneling conditions: (A) 675.1 mV and 299.4 pA; (C) 566.7 mV and 515.5 pA. Statistical histograms of the peptide length of (B) G5 and (D) G6 measured from the STM images. Both statistical histograms were fitted by Gaussian distribution (red lines) with the most probable length of the measured strands ca. 3.2 nm and 3.6 nm respectively.

Fig. 2. The cluster analysis of conformations of (A) G5 and (B) G6 in solution from the last 10 ns molecular simulation trajectories (1000 structures each). Conformations with high similarity are clustered into one group with the numbers in each group shown in the histograms. Side views of the G5-graphite system (C) and the G6-graphite (D) systems at 0 ns (top) and 60 ns (bottom) respectively, with the G6 having two dominant conformations in the aqueous solution.

Fig. 3. All-atom MD simulation results of peptide G6 adsorption on the HOPG surface. (A) Top and side view of the G6 and graphite system at 0 ns. The two most probable peptide conformations from clustering analysis of G6 MD simulations in solution are shown in green and blue. The backbones and the side chains of G6 are shown in balls and sticks. (B) Distances as a function of simulation time from the centroid of G6 to graphite surface (left panel) and from the first to the last Cα atoms of the G6 peptide (right panel) with the two most probable conformations shown in green and blue. The left panel shows the adsorption processes of both conformations of G6 started at the position as in (A) which is 14 Å above the HOPG surface and ended at around 3 Å at the steady state. The right panel demonstrates that the end-to-end distances of the conformations of both G6 started as in (A), which are around 10 and 14 Å, respectively, and become extended after adsorption.

Fig. 4. MD simulations and DFT calculations of G6 assembly. (A) Top view of G6 assembly on graphite surface at t = 200 ns of independent 200 ns MD simulations. Pristine G6 oligomers adopt an anti-parallel conformation. (B) The optimized model of G6 assembly. The image in the red box shows the details of the model, with hydrogen bonds highlighted. The conformations of the co-assembly oligomers are parallel.