Ab initio simulations of peptide-mineral interactions

We performed Car-Parrinello Molecular Dynamics (CPMD) simulations of two amino acids, aspartic acid (Asp) and phophoserine (pSer), on a calcium oxalate monohydrate (COM) surface as a model of the interactions of phosphoproteins with biominerals. In our earlier work using in vitro experiments and classical Molecular Dynamics (MD) simulations we have demonstrated the importance of phosphorylation of serine on the interactions of osteopontin (OPN) with COM. We used configurations from our previous classical MD simulations as a starting point for the ab initio simulations. In the case of Asp we found that the a-carboxyl and amine groups form temporary close contacts with the surface. For the dipeptide Asp-pSer the carboxyl groups form permanent close contacts with the surface and the distances of its other functional groups do not vary much. We show how the interaction of carboxyl groups with COM crystal is established and confirm the importance of phosphorylation in mediating the interactions between COM surfaces and OPN. Keywords: Molecular dynamics; Ab initio; Car-Parrinello; Osteopontin; Calcium oxalate monohydrate; Aspartic acid; Phosphoserin

Effect of oxidation on POPC lipid bilayers:Anionic carboxyl group plays a major role

Phospholipids with unsaturated acyl chains are major targets of reactive oxygen species leading to formation of oxidized lipids. Oxidized phospholipids have a pronounced role in cell membrane damage. We investigated the effect of oxidation on physiological properties of phospholipid bilayers using atomistic molecular dynamics simulations. We studied phospholipid bilayer systems of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and its two stable oxidized products, 1-palmitoyl-2-(9′-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PoxnoPC) and 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC). Structural properties of the POPC lipid bilayer upon the addition of PoxnoPC or PazePC with concentration ranging from 10% to 30% were described. The key finding is that PazePC lipids bend their polar tails toward the bilayer-water interface whereas PoxnoPC lipids orient their tail toward the bilayer interior. The bilayer thickness decreases such that the thickness reduction in bilayers containing PazePC is stronger than in bilayers containing PoxnoPC. The average area per lipid decreases with a stronger effect in bilayers containing PoxnoPC. The addition of PoxnoPC makes both POPC acyl chains slightly more ordered whereas the addition of PazePC reduces the order in the two POPC acyl chains. These structural changes lead to an enhancement in the permeabilities of the bilayers containing these two oxidized products depending on the type, and the amount of oxidation. This enhancement can be achieved with a lower concentration of PazePC (10% or 15%), whereas a higher concentration of PoxnoPC (20%) is required to achieve an apparent enhancement in permeability. While the permeability of bilayers containing PazePC is higher than bilayers containing PoxnoPC in the 10-20% concentration range, by increasing the concentration of the oxidized products to higher than 20%, permeability of the bilayers containing PazePC is reduced such that it is slightly smaller than those containing PoxnoPC.</p

Nonlinear driven response of a phase-field crystal in a periodic pinning potential

We study numerically the phase diagram and the response under a driving force of the phase field crystal model for pinned lattice systems introduced recently for both one- and two-dimensional systems. The model describes the lattice system as a continuous density field in the presence of a periodic pinning potential, allowing for both elastic and plastic deformations of the lattice. We first present results for phase diagrams of the model in the absence of a driving force. The nonlinear response to a driving force on an initially pinned commensurate phase is then studied via overdamped dynamic equations of motion for different values of mismatch and pinning strengths. For large pinning strength the driven depinning transitions are continuous, and the sliding velocity varies with the force from the threshold with power-law exponents in agreement with analytical predictions. Transverse depinning transitions in the moving state are also found in two dimensions. Surprisingly, for sufficiently weak pinning potential we find a discontinuous depinning transition with hysteresis even in one dimension under overdamped dynamics. We also characterize structural changes of the system in some detail close to the depinning transition

Hydrophobicity : effect of density and order on water's rotational slowing down

Ab initio molecular dynamics (AIMD) simulations of over 4.5 ns were performed in the temperature range of T = 260–350 K with van der Waals corrections to investigate the relationship between local water density and tetrahedral order in bulk water and in the presence of a hydrophobe, tetramethylurea (TMU). We demonstrate that in bulk water, defects consisting of 5- and higher coordinated water are a major contributor to dynamics. Close to a hydrophobe, 3-coordinated defects take over. The co-existence of these defects gives rise to very different local densities. We propose that the slowing down of rotational motion close to a hydrophobe is induced by an interplay between density and order with the slowing down decreasing in the following order: (i) low-density ordered-water, (ii) normal-density ordered-water, (iii) high-density ordered-water and (iv) disordered-water. The proportions of these water environments vary with temperature. These local environments also support the idea of water's polymorphism, i.e., the existence of the high- and low-density states in supercooled water

Cell aggregation : packing soft grains

Cellular aggregates may be considered as collections of membrane enclosed units with a pressure difference between the internal and external liquid phases. Cells are kept together by membrane adhesion and/or confined space compression. Pattern formation and, in particular, intercellular spacing have important roles in controlling solvent diffusion within such aggregates. A physical approach is used to study generic aspects of cellular packings in a confined space. Average material properties are derived from the free energy. The appearance of penetrating intercellular void channels is found to be critically governed by the cell wall adhesion mechanisms during the formation of dense aggregates. A fully relaxed aggregate efficiently hinders solvent diffusion at high hydrostatic pressures, while a small fraction (~0.1) of adhesion related packing frustration is sufficient for breaking such a blockage even at high a pressure

Cell aggregation : packing soft grains

Cellular aggregates may be considered as collections of membrane enclosed units with a pressure difference between the internal and external liquid phases. Cells are kept together by membrane adhesion and/or confined space compression. Pattern formation and, in particular, intercellular spacing have important roles in controlling solvent diffusion within such aggregates. A physical approach is used to study generic aspects of cellular packings in a confined space. Average material properties are derived from the free energy. The appearance of penetrating intercellular void channels is found to be critically governed by the cell wall adhesion mechanisms during the formation of dense aggregates. A fully relaxed aggregate efficiently hinders solvent diffusion at high hydrostatic pressures, while a small fraction (~0.1) of adhesion related packing frustration is sufficient for breaking such a blockage even at high a pressure

Agent-based modelling of glucose transport

A constant supply of glucose is vital for life. Excessive and insufficient amounts can be detrimental to the health of the cell and leads to a variety of complications in the long run. However, due to the polarized nature of glucose molecules, a family of glucose transporters are required for transport across the cell’s plasma membrane. In this paper, the glucose transporter protein GLUT1 is studied using two modelling methods: a simple system of differential equations and an object oriented agent-based model. The latter approach incorporates elements of biology and communication between components into the system, yet remains relatively easy to implement. Furthermore, it yields results which are in agreement with both experimental observations and the qualitative observations of more complex mathematical models of other glucose transporters. Keywords: ordinary differential equations, pi calculus, SPiM, glucose transport, GLUT1, stochastic processes, agent-based modelling

Molecular dynamics simulation of water permeation through the alpha-hemolysin channel

The alpha-hemolysin (AHL) nanochannel is a non-selective channel that allows for uncontrolled transport of small molecules across membranes leading to cell death. Although it is a bacterial toxin, it has promising applications, ranging from drug delivery systems to nano-sensing devices. This study focuses on the transport of water molecules through an AHL nanochannel using molecular dynamics (MD) simulations. Our results show that AHL can quickly transport water across membranes. The first-passage time approach was used to estimate the diffusion coefficient and the mean exit time. To study the energetics of transport, the potential of mean force (PMF) of a water molecule along the AHL nanochannel was calculated. The results show that the energy barriers of water permeation across a nanopore are always positive along the channel and the values are close to thermal energy (kBT). These findings suggest that the observed quick permeation of water is due to small energy barriers and a hydrophobic inner channel surface resulting in smaller friction. We speculate that these physical mechanisms are important in how AHL causes cell death. Keywords: Alpha hemolysin Molecular dynamics simulations Water permeation Biological membrane Lipid bilaye

Aster formation and rupture transition in semi-flexible fiber networks with mobile cross-linkers

Fibrous active network structures whose properties are regulated by motor proteins, or simply motors, are fundamental to life. Here, a full elastic and three dimensional model for such networks and motors is presented. The effects of surface anchoring are accounted for and we demonstrate that for unidirectional motors two basic contractile phases emerge in these systems. The transition is governed by a single parameter (tb/tc) which is the ratio of the breaking strain (tb) and the motility limiting strain (tc) of the motors. For tb/tc [less, similar] 2 and clamped boundaries, the network ruptures and formation of local asters occurs with a high density of motors at the centre and the fibers radially spanning out. This phase displays contraction strain during the formation of asters but the network stress is relaxed once the asters have emerged, demonstrating that the formation of aster-like structures provides a mechanism for stress relaxation. For 2.7 [less, similar] tb/tc the network remains intact, but reaches a force equilibrium with a high contraction strain in the case of clamped boundaries. Between these two limits the network is partly ruptured. Experimental measurements (e.g. J. T. Nishizaka, H. Miyata, H. Yoshikawa, S. Ishiwata and K. Kinosita Jr., Nature, 1995, 377, 251 and J. F. Finer, R. M. Simmons, J. A. Spudich, Nature, 1994, 368, 113) indicate that actin filament and myosin motors interact with tb/tc ˜ 2.7 which is right at the limit of motor induced fracture for a random network, indicating that e.g. a cytoskeleton with active myosin is susceptible to rupture. This is perhaps not a coincidence and may well be an important factor contributing to cellular dynamics. In the case of free boundaries the network collapses onto one single aster. We also show that the distribution of energy on the motors is a power-law, below the motility limit energy, with the exponent -0.5

Structural properties of ionic detergent aggregates : a large-scale molecular dynamics study of sodium dodecyl sulfate

The properties of sodium dodecyl sulfate (SDS) aggregates were studied through extensive molecular dynamics simulations with explicit solvent. First, we provide a parametrization of the model within Gromacs. Then, we probe the kinetics of aggregation by starting from a random solution of SDS molecules and letting the system explore its kinetic pathway during the aggregation of multiple units. We observe a structural transition for the surfactant aggregates brought upon by a change in temperature. Specifically, at low temperatures, the surfactants form crystalline aggregates, whereas at elevated temperatures, they form micelles. We also investigate the dependence of aggregation kinetics on surfactant concentration and report on the molecular level structural changes involved in the transition