On the adsorption of magnetite nanoparticles on lysozyme amyloid fibrils.

An adsorption of magnetic nanoparticles (MNP) from electrostatically stabilized aqueous ferrofluids on amyloid fibrils of hen egg white lysozyme (HEWL) in 2mg/mL acidic dispersions have been detected for the MNP concentration range of 0.01-0.1vol.%. The association of the MNP with amyloid fibrils has been characterized by transmission electron microscopy (TEM), small-angle X-ray scattering (SAXS) and magneto-optical measurements. It has been observed that the extent of adsorption is determined by the MNP concentration. When increasing the MNP concentration the formed aggregates of magnetic particles repeat the general rod-like structure of the fibrils. The effect is not observed when MNP are mixed with the solution of lysozyme monomers. The adsorption has been investigated with the aim to clarify previously found disaggregation activity of MNP in amyloid fibrils dispersions and to get deeper insight into interaction processes between amyloids and MNP. The observed effect is also discussed with respect to potential applications for ordering lysozyme amyloid fibrils in a liquid crystal phase under external magnetic fields.

Collapse and hybridization of RNA: view from replica technique approach.

The replica technique method is applied to investigate the kinetic behavior of the coarse-grained model for the RNA molecule. A non-equilibrium phase transition of second order between the glassy phase and the ensemble of freely fluctuating structures has been observed. The non-equilibrium steady state is investigated as well and the thermodynamic characteristics of the system have been evaluated. The non-equilibrium behavior of the specific heat is discussed. Based on our analysis, we point out the state in the kinetic pathway in which the RNA molecule is most prone to hybridization.

Long charged macromolecule in an entropic trap with rough surfaces.

The kinetics of the flux of a charged macromolecular solution through an environment of changing geometry with wide and constricted regions is investigated analytically. A model device consisting of alternating deep and shallow slits known as an "entropic trap" is used to represent the environment. The flux is supported by the external electrostatic field. The "wormlike chain" model is used for the macromolecule (dsDNA in the present study). The chain entropy in both the deep and the shallow slits, the work by the electric field, and the energy of the elastic bending of the chain are taken into account accurately. Based on the calculated free energy, the kinetics and the scaling behavior of the chain escaping from the entropic trap are studied. We find that the escape process occurs in two kinetic stages with different time scales and discuss the possible influence of the surface roughness. The scope of the accuracy of the proposed model is discussed.

Enveloping triangulation method for detecting internal cavities in proteins and algorithm for computing their surface areas and volumes.

Detection and quantitative characterization of the internal cavities in proteins remain an important topic in studying protein structure and function. Here we propose a new analytical method for detecting the existence of cavities in proteins. The method is based on constructing the special enveloping triangulation enclosing the cavities. Based on this method, we develop an algorithm and a fortran package, CAVE, for computing volumes and surface areas of cavities in proteins. We first test our method and algorithm in some artificial systems of spheres and find that the calculated results are consistent with exact results. Then we apply the package to compute volumes and surface areas of cavities for some protein structures in the Protein Data Bank. We compare our calculated results with those obtained by some other methods and find that our approach is reliable.

RNA folding in the presence of counterions.

We present a general thermodynamic picture of the folding of RNA-like heteropolymer based on the basic physical principles. The Hamiltonian of the model includes all characteristic interactions explicitly. A particular attention is paid to the electrostatic interactions whose role in the RNA folding is known to be crucial. In this paper we study RNA folding with the full Hamiltonian and describe the spin-glass behavior on the level of tertiary structure. We show that formation of the stable tertiary structure is possible in the random RNA-like molecule. By including into the model the nonspecific interactions of the RNA molecule with counterions, we derive the logarithmic dependencies of the melting and freezing temperatures on the ion concentration, which is consistent with experimental data [R. Shiman and D. E. Draper, J. Mol. Biol. 302, 79 (2000)]. We also infer that the large RNA folds slower than the hierarchical model predicts, which was observed in the experiments.

Random sequences with power-law correlations exhibit proteinlike behavior.

We use a replica approach to investigate the thermodynamic properties of the random heteropolymers with persistent power-law correlations in monomer sequence. We show that this type of sequences possess proteinlike properties. In particular, we show that they can fold into stable unique three-dimensional structure (the "native" structure, in protein terminology) through two different types of pathways. One is a fast folding pathway and leads directly to the native structure. Another one, a more slower pathway, passes through the microphase separated (MPS) state and includes a number of intermediate glassy states. The scale and the magnitude of the MPS are calculated. The frozen state can be reached only by sequences with weak long-range correlations. The critical value for the correlation exponent is found, above which (strong correlations) freezing is impossible.

Efficient combination of Wang-Landau and transition matrix Monte Carlo methods for protein simulations.

An efficient combination of the Wang-Landau and transition matrix Monte Carlo methods for protein and peptide simulations is described. At the initial stage of simulation the algorithm behaves like the Wang-Landau algorithm, allowing to sample the entire interval of energies, and at the later stages, it behaves like transition matrix Monte Carlo method and has significantly lower statistical errors. This combination allows to achieve fast convergence to the correct values of density of states. We propose that the violation of TTT identities may serve as a qualitative criterion to check the convergence of density of states. The simulation process can be parallelized by cutting the entire interval of simulation into subintervals. The violation of ergodicity in this case is discussed. We test the algorithm on a set of peptides of different lengths and observe good statistical convergent properties for the density of states. We believe that the method is of general nature and can be used for simulations of other systems with either discrete or continuous energy spectrum.

Folding of the protein domain hbSBD.

The folding of the alpha-helix domain hbSBD of the mammalian mitochondrial branched-chain alpha-ketoacid dehydrogenase complex is studied by the circular dichroism technique in absence of urea. Thermal denaturation is used to evaluate various thermodynamic parameters defining the equilibrium unfolding, which is well described by the two-state model with the folding temperature T(F) = 317.8 +/- 1.95 K and the enthalpy change DeltaH(G) = 19.67 +/- 2.67 kcal/mol. The folding is also studied numerically using the off-lattice coarse-grained Go model and the Langevin dynamics. The obtained results, including the population of the native basin, the free-energy landscape as a function of the number of native contacts, and the folding kinetics, also suggest that the hbSBD domain is a two-state folder. These results are consistent with the biological function of hbSBD in branched-chain alpha-ketoacid dehydrogenase.

A new analytical method for computing solvent-accessible surface area of macromolecules and its gradients.

In the calculation of thermodynamic properties and three-dimensional structures of macromolecules, such as proteins, it is important to have an efficient algorithm for computing the solvent-accessible surface area of macromolecules. Here, we propose a new analytical method for this purpose. In the proposed algorithm we consider the transformation that maps the spherical circles formed by intersection of the atomic surfaces in three-dimensional space onto the circles on a two-dimensional plane, and the problem of computing the solvent-accessible surface area is reduced to the problem of computing the corresponding curve integrals on the plane. This allows to consider only the integrals along the circular trajectories on the plane. The algorithm is suitable for parallelization. Testings on many proteins as well as the comparison to the other analogous algorithms have shown that our method is accurate and efficient.