Using steered molecular dynamics simulations and single-molecule force spectroscopy to guide the rational design of biomimetic modular polymeric materials

Abstract

This article describes results on using steered molecular dynamics (SMD) simulations and experimental single molecule force spectroscopy (SMFS) to investigate the relationship between hydrogen bonding and mechanical stability of a series of homodimeric β-sheet mimics. The dimers consisting of 4, 6, and 8 H-bonding sites were modeled in explicit chloroform solvent and the rupture force was studied using constant velocity SMD. The role of solvent structuring on the conformation of the dimers was analyzed and showed no significant contribution of chloroform molecules in the rupture event. The simulated stability of the dimers was validated by force data obtained with atomic force microscopy (AFM)-based SMFS in toluene. The computational model for the 8H dimer also offered insight into a possible mismatched dimer intermediate that may contribute to the lower than expected mechanical stability observed by single molecule AFM force studies. In addition, atomic level analysis of the rupture mechanism verified the dependence of mechanical strength on pulling trajectory due to the directional nature of chemical bonding under an applied force. The knowledge gained from this basic study will be used to guide further design of modular polymers having folded nanostructures through strategic programming of weak, non-covalent interactions into polymer backbones.

A Highly Stretchable and Autonomous Self‐Healing Polymer Based on Combination of Pt···Pt and π–π Interactions

“…For PDMS‐L, only one stretching force of ≈77 pN was found from the rupture force histogram (Figure c). This force should be ascribed to hydrogen bonding between amide groups in the molecular chains, similar to that of the peptidomimetics consists of aromatic nuclei and amides . In contrast, three force peaks, with the force of ≈69, 127, and 226 pN, respectively, were observed from the rupture force histogram of PDMS‐PtL (Figure d).…”

Molecular dynamics simulation exploration of unfolding and refolding of a ten-amino acid miniprotein

“…However, we have known little about the details of folding and unfolding process for CLN025 yet. In this paper, we study the unfolding of CLN025 by mechanical stretching using steered molecular dynamics (SMD) simulation, which mimics AFM experiment and reveals the molecular mechanisms underlying mechanical function (Guzmán et al 2008(Guzmán et al , 2009Lu and Schulten 1999;Hamdi et al 2008;Rief et al 1997;Lim et al 2008;Zeng et al 2010). Because of computational limits, the pulling velocities used in SMD are orders of magnitude higher than those in an AFM experiment, leading to drastic overestimation of the unfolding forces.…”

Application of Graphene as a Nanoindenter Interacting with Phospholipid Membranes—Computer Simulation Study

“…The indentation/withdrawal rates of 1 and 2 m/s are in general much higher than those used in experimental studies, such as atomic force microscopy or single-molecule force spectroscopy. 35 , 36 These choices are a result of the compromise between computation time and a faithful reproduction of membrane behavior. The rates are, however, comparable to those in previous studies 25 , 26 , 35 , 37 , 38 and with those in SMD simulations of other biological phenomena, such as protein folding.…”