Confinement-Dependent Friction in Peptide Bundles

Abstract

Friction within globular proteins or between adhering macromolecules crucially determines the kinetics of protein folding, the formation, and the relaxation of self-assembled molecular systems. One fundamental question is how these friction effects depend on the local environment and in particular on the presence of water. In this model study, we use fully atomistic MD simulations with explicit water to obtain friction forces as a single polyglycine peptide chain is pulled out of a bundle of k adhering parallel polyglycine peptide chains. The whole system is periodically replicated along the peptide axes, so a stationary state at prescribed mean sliding velocity V is achieved. The aggregation number is varied between k = 2 (two peptide chains adhering to each other with plenty of water present at the adhesion sites) and k = 7 (one peptide chain pulled out from a close-packed cylindrical array of six neighboring peptide chains with no water inside the bundle). The friction coefficient per hydrogen bond, extrapolated to the viscous limit of vanishing pulling velocity V → 0, exhibits an increase by five orders of magnitude when going from k = 2 to k = 7. This dramatic confinement-induced friction enhancement we argue to be due to a combination of water depletion and increased hydrogen-bond cooperativity.

Viscous Friction between Crystalline and Amorphous Phase of Dragline Silk

“…The reason is that the data does not fall into the turnover regime into the viscous limit, as we do not achieve sufficiently long time scales in our MD simulations. However, the fitting was robust with respect to variations of , and the best fitting values fall into the previously obtained range of values [14],[21],[22]. Interestingly, the bond strength we obtain here is lower than the one we obtained within silk peptide bundles, which reflects the lower hydrogen bond density at the partially hydrophobic crystal surfaces.…”

“…Molecular friction has been systematically assessed for proteins at inorganic (hydrophobic or hydrophilic) surfaces using both single molecule force spectroscopy and MD simulations [20] – [22] . We here focus on the friction between the amorphous and crystalline domains of dragline silk fibers.…”

Effects of electrostatic interactions on ligand dissociation kinetics

“…6, we show the simulation results for the explicit electrostatic simulations only for various nonelectrostatic binding energies, since we have shown in the previous sections that implicit treatment cannot provide correct physical environment for unbinding. In the simulation, we vary the strength of the non-electrostatic binding energy per bead so that we can scan energy ranges around 10 k B T total, which is the typical molecular binding energies [10,34,46]. Our simulations reveal various regimes for unbinding events.…”

Principal component analysis of nonequilibrium molecular dynamics simulations

“…Since ∆G(s) is considerably lower than the average work W (s) , the stretching of state B into helix A with velocity v c = 1 m/s generates considerable irreversible heat via intramolecular friction. [59][60][61][62][63] Having verified that the TMD simulations correctly reproduce the free energy profile ∆G(s), we are in a position to consider to what extent TMD allows us to predict the free energy along a general reaction coordinate x. As suitable coordinates we choose the first two principal components V eq,B A 1 and V eq,B A 2 obtained from dPCA+, which was performed for all unbiased trajectory points that lie in the interval 1.1 nm ≤ s ≤ 2.1 nm.…”