Nanoscale Structure and Elasticity of Pillared DNA Nanotubes

We present an atomistic model of pillared DNA nanotubes (DNTs) and their elastic properties which will facilitate further studies of these nanotubes in several important nanotechnological and biological applications. In particular, we introduce a computational design to create an atomistic model of a 6-helix DNT (6HB) along with its two variants, 6HB flanked symmetrically by two double helical DNA pillars (6HB+2) and 6HB flanked symmetrically by three double helical DNA pillars (6HB+3). Analysis of 200 ns all-atom simulation trajectories in the presence of explicit water and ions shows that these structures are stable and well behaved in all three geometries. Hydrogen bonding is well maintained for all variants of 6HB DNTs. We calculate the persistence length of these nanotubes from their equilibrium bend angle distributions. The values of persistence length are ~10 {\mu}m, which is 2 orders of magnitude larger than that of dsDNA. We also find a gradual increase of persistence length with an increasing number of pillars, in quantitative agreement with previous experimental findings. To have a quantitative understanding of the stretch modulus of these tubes we carried out nonequilibrium Steered Molecular Dynamics (SMD). The linear part of the force extension plot gives stretch modulus in the range of 6500 pN for 6HB without pillars which increases to 11,000 pN for tubes with three pillars. The values of the stretch modulus calculated from contour length distributions obtained from equilibrium MD simulations are similar to those obtained from nonequilibrium SMD simulations. The addition of pillars makes these DNTs very rigid.Comment: Published in ACS Nan

Atomistic to continuum model for studying mechanical properties of RNA nanotubes

With rapid advancements in the emerging field of RNA nanotechnology, its current and potential applications, new important problems arise in our quest to better understand properties of RNA nanocomplexes. In this paper, our focus is on the modeling of RNA nanotubes which are important for many biological processes. These RNA complexes are also important for human beings, with their theurapeuti- cal and biomedical applications discussed vigorously in the literature over the recent years. Here, we develop a continuum model of RNA nanotubes, originally obtained from self assembly of RNA building blocks in the molecular dynamics simulation. Based on the finite element method, we calculate the elastic properties of these nanostructures and provide a relationship between stress and strain induced in the RNA nanotube. We also analyze the variations in the displacement vector along the assembly axis for RNA nanotubes of different sizes. In particular, we show that os- cillations in the amplitudes of strains and displacements significantly differ for such RNA nanotubes. These findings are discussed in the context of atomistic simulations and experimental results in this field

Translocation and encapsulation of siRNA inside carbon nanotubes

We report spontaneous translocation of small interfering RNA (siRNA) inside carbon nanotubes (CNTs) of various diameters and chirality using all atom molecular dynamics (MD) simulations with explicit solvent. We use Umbrella sampling method to calculate the free energy landscape of the siRNA entry and translocation event. Free energy profiles shows that siRNA gains free energy while translocating inside CNT and barrier for siRNA exit from CNT ranges from 40 to 110 kcal/mol depending on CNT chirality and salt concentration. The translocation time \tau decreases with the increase of CNT diameter with a critical diameter of 24 \AA for the translocation. In contrast, double strand DNA (dsDNA) of the same sequence does not translocate inside CNT due to large free energy barrier for the translocation. This study helps in understanding the nucleic acid transport through nanopores at microscopic level and may help designing carbon nanotube based sensor for siRNA.Comment: Accepted for the Journal of Chemical Physics; 24 pages, 6 figures and 1 tabl

Dimensionality of Carbon Nanomaterials Determines the Binding and Dynamics of Amyloidogenic Peptides: Multiscale Theoretical Simulations

Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly, possibly interfering with the development of protein misfolding diseases such as Alzheimer's, Parkinson's and prion disease caused by aggregation and fibril formation of amyloid-prone proteins. We employ classical molecular dynamics simulations and large-scale density functional theory calculations to investigate the effects of nanomaterials on the structure, dynamics and binding of an amyloidogenic peptide apoC-II(60-70). We show that the binding affinity of this peptide to carbonaceous nanomaterials such as C60, nanotubes and graphene decreases with increasing nanoparticle curvature. Strong binding is facilitated by the large contact area available for π-stacking between the aromatic residues of the peptide and the extended surfaces of graphene and the nanotube. The highly curved fullerene surface exhibits reduced efficiency for π-stacking but promotes increased peptide dynamics. We postulate that the increase in conformational dynamics of the amyloid peptide can be unfavorable for the formation of fibril competent structures. In contrast, extended fibril forming peptide conformations are promoted by the nanotube and graphene surfaces which can provide a template for fibril-growth

Electrokinetic Lattice Boltzmann solver coupled to Molecular Dynamics: application to polymer translocation

We develop a theoretical and computational approach to deal with systems that involve a disparate range of spatio-temporal scales, such as those comprised of colloidal particles or polymers moving in a fluidic molecular environment. Our approach is based on a multiscale modeling that combines the slow dynamics of the large particles with the fast dynamics of the solvent into a unique framework. The former is numerically solved via Molecular Dynamics and the latter via a multi-component Lattice Boltzmann. The two techniques are coupled together to allow for a seamless exchange of information between the descriptions. Being based on a kinetic multi-component description of the fluid species, the scheme is flexible in modeling charge flow within complex geometries and ranging from large to vanishing salt concentration. The details of the scheme are presented and the method is applied to the problem of translocation of a charged polymer through a nanopores. In the end, we discuss the advantages and complexities of the approach

Hamiltonian dynamics, nanosystems, and nonequilibrium statistical mechanics

An overview is given of recent advances in nonequilibrium statistical mechanics on the basis of the theory of Hamiltonian dynamical systems and in the perspective provided by the nanosciences. It is shown how the properties of relaxation toward a state of equilibrium can be derived from Liouville's equation for Hamiltonian dynamical systems. The relaxation rates can be conceived in terms of the so-called Pollicott-Ruelle resonances. In spatially extended systems, the transport coefficients can also be obtained from the Pollicott-Ruelle resonances. The Liouvillian eigenstates associated with these resonances are in general singular and present fractal properties. The singular character of the nonequilibrium states is shown to be at the origin of the positive entropy production of nonequilibrium thermodynamics. Furthermore, large-deviation dynamical relationships are obtained which relate the transport properties to the characteristic quantities of the microscopic dynamics such as the Lyapunov exponents, the Kolmogorov-Sinai entropy per unit time, and the fractal dimensions. We show that these large-deviation dynamical relationships belong to the same family of formulas as the fluctuation theorem, as well as a new formula relating the entropy production to the difference between an entropy per unit time of Kolmogorov-Sinai type and a time-reversed entropy per unit time. The connections to the nonequilibrium work theorem and the transient fluctuation theorem are also discussed. Applications to nanosystems are described.Comment: Lecture notes for the International Summer School Fundamental Problems in Statistical Physics XI (Leuven, Belgium, September 4-17, 2005

Effect of water models on transmembrane self-assembled cyclic peptide nanotubes

Self-assembling cyclic peptide nanotubes can form nanopores when they are inserted in lipid bilayers, acting as ion and/or water permeable channels. In order to improve the versatility of these systems, it is possible to specifically design cyclic peptides with a combination of natural and non-natural amino acids, enabling the control of the nature of the inner cavity of the channels. Here, the behavior of two types of self-assembling peptide motifs, alternating α-amino acids with γ- or δ-aminocycloalkanecarboxylic acids, is studied via molecular dynamics (MD) simulations. The behavior of water molecules in nanopores is expected to affect the properties of these channels and therefore merits detailed examination. A number of water models commonly used in MD simulations have been validated by how well they reproduce bulk water properties. However, it is less clear how these water models behave in the nanoconfined condition inside a channel. The behavior of four different water models—TIP3P, TIP4P, TIP4P/2005, and OPC—are evaluated in MD simulations of self-assembled cyclic peptide nanotubes of distinct composition and diameter. The dynamic behavior of the water molecules and ions in these designed artificial channels depends subtly on the water model used. TIP3P water molecules move faster than those of TIP4P, TIP4P/2005, and OPC. This demeanor is clearly observed in the filling of the nanotube, in water diffusion within the pore, and in the number and stability of hydrogen bonds of the peptides with water. It was also shown that the water model influences the simulated ion flux through the nanotubes, with TIP3P producing the greatest ion flux. Additionally, the two more recent models, TIP4P/2005 and OPC, which are known to reproduce the experimental self-diffusion coefficient of bulk water quite well, exhibit very similar results under the nanoconfined conditions studied here. Because none of these models have been parametrized specifically for waters confined in peptide nanotubes, this study provides a point of reference for further validationThis work was supported by the Spanish Agencia Estatal de Investigación (AEI) and the ERDF (CTQ2016-78423-R, PID2019-111126RB-100, and RTI2018-098795-A-I00) and by the Xunta de Galicia and the ERDF (ED431F 2020/05, ED431C 2017/25, and Centro singular de investigación de Galicia accreditation 2016-2019, ED431G/09). M.C. thanks Xunta de Galicia for a predoctoral fellowship (ED481A-2017/068). R.G.-F. thanks Ministerio de Ciencia, Innovación y Universidades for a Ramón y Cajal contract (RYC-2016- 20335). Research in MSPS’s group is supported by EPSRC (EP/R004722/1; EP/V010948/1) BBSRC (BB/R00126X/1) and Wellcome Trust (208361/Z/17/Z)S