First-Passage Time Distribution and Non-Markovian Diffusion Dynamics of Protein Folding

We study the kinetics of protein folding via statistical energy landscape theory. We concentrate on the local-connectivity case, where the configurational changes can only occur among neighboring states, with the folding progress described in terms of an order parameter given by the fraction of native conformations. The non-Markovian diffusion dynamics is analyzed in detail and an expression for the mean first-passage time (MFPT) from non-native unfolded states to native folded state is obtained. It was found that the MFPT has a V-shaped dependence on the temperature. We also find that the MFPT is shortened as one increases the gap between the energy of the native and average non-native folded states relative to the fluctuations of the energy landscape. The second- and higher-order moments are studied to infer the first-passage time (FPT) distribution. At high temperature, the distribution becomes close to a Poisson distribution, while at low temperatures the distribution becomes a L\'evy-like distribution with power-law tails, indicating a non-self-averaging intermittent behavior of folding dynamics. We note the likely relevance of this result to single-molecule dynamics experiments, where a power law (L\'evy) distribution of the relaxation time of the underlined protein energy landscape is observed.Comment: 26 pages, 10 figure

Diffusion Dynamics, Moments, and Distribution of First Passage Time on the Protein-Folding Energy Landscape, with Applications to Single Molecules

We study the dynamics of protein folding via statistical energy-landscape theory. In particular, we concentrate on the local-connectivity case with the folding progress described by the fraction of native conformations. We obtain information for the first passage-time (FPT) distribution and its moments. The results show a dynamic transition temperature below which the FPT distribution develops a power-law tail, a signature of the intermittency phenomena of the folding dynamics. We also discuss the possible application of the results to single-molecule dynamics experiments

Studies on electrostatic interactions of colloidal particles under two-dimensional confinement

We study the effective electrostatic interactions between a pair of charged colloidal particles without salt ions while the system is confined in two dimensions. In particular we use a simplified model to elucidate the effects of rotational fluctuations in counterion distribution. The results exhibit effective colloidal attractions under appropriate conditions. Meanwhile, long-range repulsions persist over most of our studied cases. The repulsive forces arise from the fact that in two dimensions the charged colloids cannot be perfectly screened by counterions, as the residual quadrupole moments contribute to the repulsions at longer range. And by applying multiple expansions we find that the attractive forces observed at short range are mainly contributed from electrostatic interactions among higher-order electric moments. We argue that the scenario for attractive interactions discussed in this work is applicable to systems of charged nanoparticles or colloidal solutions with macroions.Comment: 23 pages, 11 figures, 1 tabl

SCOZA for Monolayer Films

We show the way in which the self-consistent Ornstein-Zernike approach (SCOZA) to obtaining structure factors and thermodynamics for Hamiltonian models can best be applied to two-dimensional systems such as thin films. We use the nearest-neighbor lattice gas on a square lattice as an illustrative example.Comment: 10 pages, 5 figure

Effects of overexpression of IL-10, IL-12, TGF-β and IL-4 on allergen induced change in bronchial responsiveness

BACKGROUND: An increasing prevalence of allergic diseases, such as atopic dermatitis, allergic rhinitis and bronchial asthma, has been noted worldwide. Allergic asthma strongly correlates with airway inflammation caused by the unregulated production of cytokines secreted by allergen-specific type-2 T helper (Th2) cells. This study aims to explore the therapeutic effect of the airway gene transfer of IL-12, IL-10 and TGF-β on airway inflammation in a mouse model of allergic asthma. METHODS: BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA and challenged by nebulized OVA. Different cytokine gene plasmids or non-coding vector plasmids were instilled daily into the trachea up to one day before the inhalatory OVA challenge phase. RESULTS: Intratracheal administration of IL-10, IL-12 or TGF-β can efficiently inhibit antigen-induced airway hyper-responsiveness and is able to largely significantly lower the number of eosinophils and neutrophils in bronchoalveolar lavage fluid of ovalbumin (OVA) sensitized and challenged mice during the effector phase. Furthermore, the effect of IL-10 plasmids is more remarkable than any other cytokine gene plasmid. On the other hand, local administration of IL-4 gene plasmids before antigen challenge can induce severe airway hyper-responsiveness (AHR) and airway eosinophilia. CONCLUSION: Our data demonstrated that anti- inflammatory cytokines, particularly IL-10, have the therapeutic potential for the alleviation of airway inflammation in murine model of asthma