Performance of Different Force Fields in Force Probe Simulations

We present detailed force probe molecular dynamic simulations of mechanically interlocked dimeric calix[4]­arene–catenanes, comparing the results obtained using three different commonly used force fields (GROMOS G53a5, OPLS-AA, and AMBER GAFF). The model system is well characterized as a two-state system consisting of a closed compact and an elongated structure. Both states are stabilized by a different hydrogen-bond network, and complete separation of the dimer is prevented by the mechanical lock of the entangled aliphatic loops. The system shows fully reversible rebinding meaning that after bond rupture the system rejoins when the external force is relaxed. We present a detailed study of quantities determined in simulations using a force ramp, like the rupture force and rejoin force distributions. Additionally, we analyze the dynamics of the hydrogen-bond network. We find that the results obtained from using the different force fields qualitatively agree in the sense that always the fully reversible behavior is found. The details, like the mean rupture forces, however, do depend on the particular force field. Some of the differences observed can be traced back to differences in the strength of the hydrogen-bond networks

Determining Factors for the Unfolding Pathway of Peptides, Peptoids, and Peptidic Foldamers

We present a study of the mechanical unfolding pathway of five different oligomers (α-peptide, β-peptide, δ-aromatic-peptides, α/γ-peptides, and β-peptoids), adopting stable helix conformations. Using force-probe molecular dynamics, we identify the determining structural factors for the unfolding pathways and reveal the interplay between the hydrogen bond strength and the backbone rigidity in the stabilization of their helix conformations. On the basis of their behavior, we classify the oligomers in four groups and deduce a set of rules for the prediction of the unfolding pathways of small foldamers

Comparative Study of the Mechanical Unfolding Pathways of α- and β‑Peptides

Using molecular simulations, we analyze the unfolding pathways of various peptides. We compare the mechanical unfolding of a β-alanine’s octamer (β-HAla₈) and an α-alanine’s decamer (α-Ala₁₀). Using force-probe molecular-dynamics simulations, to induce unfolding, we show that the 3₁₄-helix formed by β-HAla₈ is mechanically more stable than the α-helix formed by α-Ala₁₀, although both structures are stabilized by six hydrogen bonds. Additionally, computations of the potential of mean force validate this result and show that also the thermal stability of the 3₁₄-helix is higher. It is demonstrated that β-HAla₈ unfolds in a two-step fashion with a stable intermediate. This is contrasted with the known single-step scenario of the unfolding of α-Ala₁₀. Furthermore, we present a study of the chain-length dependence of the mechanical unfolding pathway of the 3₁₄-helix. The calculation of the dynamic strength for oligomers with chain lengths ranging from 6 to 18 monomers shows that the unfolding pathway of helices with an integer and noninteger number of turns has <i>m</i> + 1 and <i>m</i> energy barriers, respectively, with <i>m</i> being the number of complete turns. The additional barrier for helices with an integer number of turns is shown to be related to the breaking of the N-terminus’ hydrogen bond

Hybrid Particle-Field Molecular Dynamics Simulations of Charged Amphiphiles in Aqueous Environment

<p>We develop and test specific coarse-grained models for charged amphiphilic systems such as palmitoyloleoyl phosphatidylglycerol (POPG) lipid bilayer, and sodium dodecyl sulphate (SDS) surfactant in aqueous environment, to verify the ability of the hybrid particle-field method to provide a realistic description of polyelectrolyte soft-matter systems. The intramolecular interactions are treated by a standard molecular Hamiltonian and the non-electrostatic intermolecular forces are described by density fields. Electrostatics is introduced as an additional external field obtained by a modified particle-mesh Ewald procedure. Molecular dynamics simulations indicate that the methodology is robust with respect to the choice of the relative dielectric constant, yielding the same correct qualitative behavior for a broad range of dielectric values. In particular, our methodology reproduces well the organization of the POPG bilayer, as well as the SDS concentration-dependent change in the morphology of the micelles from spherical to microtubular aggregates. </p

Hybrid Particle-Field Molecular Dynamics Simulations of Charged Amphiphiles in an Aqueous Environment

We develop and test specific coarse-grained models for charged amphiphilic systems such as palmitoyloleoylphosphatidylglycerol (POPG) lipid bilayer and sodium dodecyl sulfate (SDS) surfactant in an aqueous environment, to verify the ability of the hybrid particle-field method to provide a realistic description of polyelectrolytes. According to the hybrid approach, the intramolecular interactions are treated by a standard molecular Hamiltonian, and the nonelectrostatic intermolecular forces are described by density fields. Electrostatics is introduced as an additional external field obtained by a modified particle-mesh Ewald procedure, as recently proposed [Zhu et al. Phys. Chem. Chem. Phys. 2016, 18, 9799]. Our results show that, upon proper calibration of key parameters, electrostatic forces can be correctly reproduced. Molecular dynamics simulations indicate that the methodology is robust with respect to the choice of the relative dielectric constant, yielding the same correct qualitative behavior for a broad range of values. In particular, our methodology reproduces well the organization of the POPG bilayer, as well as the SDS concentration-dependent change in the morphology of the micelles from spherical to microtubular aggregates. The inclusion of explicit electrostatics with good accuracy and low computational cost paves the way for a significant extension of the hybrid particle-field method to biological systems, where the polyelectrolyte component plays a fundamental role for both structural and dynamical molecular properties