Organization of two kinesins in a two-dimensional microtubule network.

In intracellular active transport, molecular motors are responsible for moving biological cargo along networks of microtubules that serve as scaffolds. Cargo dynamics can be modified by different features of microtubule networks such as geometry, density, orientation modifications. Also, the dynamical behaviour of the molecular motors is determined by the microtubule network and by the individual and/or collective action of the motors.

Elastic traits of the extensible discrete wormlike chain model.

Polymer models play the special role of elucidating the elementary features describing the physics of long molecules and become essential to interpret the measurements of their magnitudes. In this work the end-to-end distance of an extensible discrete wormlike chain polymer as a function of the applied force has been calculated both numerically and analytically, the latter as an effective approximation. The numerical evaluation uses the transfer matrix formalism to obtain an exact calculation of the partition function, while the analytic derivations generalize the simple phenomenological formulas largely used up to now.

Thermal versus mechanical unfolding in a model protein.

Force spectroscopy techniques are often used to learn about the free energy landscape of single biomolecules, typically by recovering free energy quantities that, extrapolated to zero force, are compared to those measured in bulk experiments. However, it is not always clear how the information obtained from a mechanically perturbed system can be related to the information obtained using other denaturants since tensioned molecules unfold and refold along a reaction coordinate imposed by the force, which is not likely to be meaningful in its absence. Here, we explore this dichotomy by investigating the unfolding landscape of a model protein, which is unfolded first mechanically through typical force spectroscopy-like protocols and next thermally.

A physical picture for mechanical dissociation of biological complexes: from forces to free energies.

Single-molecule force spectroscopy is a powerful technique based on the application of controlled forces to macromolecules. In order to relate the measured response of the molecule to its equilibrium and dynamic properties, a suitable physical picture of the involved process is necessary. In this work, we introduce a plausible model for mechanical unbinding of some molecular complexes, based on a novel free energy profile.

Macro and nano scale modelling of water-water interactions at ambient and low temperature: relaxation and residence times.

The decay dynamics of ambient and low temperature liquid water has been investigated through all-atom molecular dynamics simulations, residence times calculations and time correlation functions from 300 K down to 243 K. Those simulations replicate the experimental value of the self-diffusion constant as a function of temperature by tuning the damping factor of the Langevin equation of motion. A stretched exponential function exp[-(t/τ)(β)] has been found to properly describe the relaxation of residence times calculated at different temperatures for solvent molecules in a nanodrop of free water modelled as a sphere of nanometric dimensions.

Role of the central cations in the mechanical unfolding of DNA and RNA G-quadruplexes.

Cations are known to mediate diverse interactions in nucleic acids duplexes but they are critical in the arrangement of four-stranded structures. Here, we use all-atom molecular dynamics simulations with explicit solvent to analyse the mechanical unfolding of representative intramolecular G-quadruplex structures: a parallel, a hybrid and an antiparallel DNA and a parallel RNA, in the presence of stabilising cations. We confirm the stability of these conformations in the presence of [Formula: see text] central ions and observe distortions from the tetrad topology in their absence.

An integrative approach for modeling and simulation of heterocyst pattern formation in cyanobacteria filaments.

Heterocyst differentiation in cyanobacteria filaments is one of the simplest examples of cellular differentiation and pattern formation in multicellular organisms. Despite of the many experimental studies addressing the evolution and sustainment of heterocyst patterns and the knowledge of the genetic circuit underlying the behavior of single cyanobacterium under nitrogen deprivation, there is still a theoretical gap connecting these two macroscopic and microscopic processes. As an attempt to shed light on this issue, here we explore heterocyst differentiation under the paradigm of systems biology.

Mesoscopic model and free energy landscape for protein-DNA binding sites: analysis of cyanobacterial promoters.

The identification of protein binding sites in promoter sequences is a key problem to understand and control regulation in biochemistry and biotechnological processes. We use a computational method to analyze promoters from a given genome. Our approach is based on a physical model at the mesoscopic level of protein-DNA interaction based on the influence of DNA local conformation on the dynamics of a general particle along the chain.

DNA overstretching transition induced by melting in a dynamical mesoscopic model.

We present a phenomenological dynamical model describing the force induced melting as responsible for the DNA overstretching transition. The denaturation mechanism is developed under the framework of the mesoscopic one-dimensional Peyrard-Bishop-Dauxois (PBD) picture which models the melting features of a polymer chain by means of a Morse potential and the stacking interaction. We find a good agreement with both the experimental overstretching curve and the asymmetric hysteretic properties with different simulation times.

Dynamical model for the full stretching curve of DNA.

We present a phenomenological dynamical model able to describe the stretching features of the curve of DNA length vs applied force. As concerns the chain, the model is based on the discrete wormlike chain model with elastic modifications, which properly describes the elongation features at low and intermediate forces. The dynamics is developed under a double-well potential with a linear term, which, at high forces, accounts for the narrow transition present in the DNA elongation (overstretching).

Tug of war of molecular motors: the effects of uneven load sharing.

We analyze theoretically the problem of cargo transport along microtubules by motors of two species with opposite polarities. We consider two different one-dimensional models previously developed in the literature: a quite widespread model which assumes equal force sharing, here referred to as the mean field model (MFM), and a stochastic model (SM) which considers individual motor-cargo links. We find that in generic situations, the MFM predicts larger cargo mean velocity, smaller mean run time and less frequent reversions than the SM.

Translocation time of periodically forced polymer chains.

In this work we study the presence of both a minimum and clear oscillations in the frequency dependence of the translocation time of a polymer described as a unidimensional Rouse chain driven by a spatially localized oscillating linear potential. The observed oscillations of the mean translocation time arise from the synchronization between the very mean translocation time and the period of the external force. We have checked the robustness of the frequency value for the minimum translocation time by changing the damping parameter, finding a very simple relationship between this frequency and the correspondent translocation time.

The influence of direct motor-motor interaction in models for cargo transport by a single team of motors.

We analyze theoretically the effects of excluded-volume interactions between motors on the dynamics of a cargo driven by multiple motors. The model considered shares much in common with others recently proposed in the literature, with the addition of direct interaction between motors and motor back steps. The cargo is assumed to follow a continuum Langevin dynamics, while individual motors evolve following a Monte Carlo algorithm based on experimentally accessible probabilities for discrete forward and backward jumps, and attachment and detachment rates.

Exploring the free energy landscape: from dynamics to networks and back.

Knowledge of the Free Energy Landscape topology is the essential key to understanding many biochemical processes. The determination of the conformers of a protein and their basins of attraction takes a central role for studying molecular isomerization reactions. In this work, we present a novel framework to unveil the features of a Free Energy Landscape answering questions such as how many meta-stable conformers there are, what the hierarchical relationship among them is, or what the structure and kinetics of the transition paths are.

Common conformational changes in flavodoxins induced by FMN and anion binding: the structure of Helicobacter pylori apoflavodoxin.

Flavodoxins, noncovalent complexes between apoflavodoxins and flavin mononucleotide (FMN), are useful models to investigate the mechanism of protein/flavin recognition. In this respect, the only available crystal structure of an apoflavodoxin (that from Anabaena) showed a closed isoalloxazine pocket and the presence of a bound phosphate ion, which posed many questions on the recognition mechanism and on the potential physiological role exerted by phosphate ions. To address these issues we report here the X-ray structure of the apoflavodoxin from the pathogen Helicobacter pylori.

A double-deletion method to quantifying incremental binding energies in proteins from experiment: example of a destabilizing hydrogen bonding pair.

The contribution of a specific hydrogen bond in apoflavodoxin to protein stability is investigated by combining theory, experiment and simulation. Although hydrogen bonds are major determinants of protein structure and function, their contribution to protein stability is still unclear and widely debated. The best method so far devised to estimate the contribution of side-chain interactions to protein stability is double mutant cycle analysis, but the interaction energies so derived are not identical to incremental binding energies (the energies quantifying net contributions of two interacting groups to protein stability).