Pavel G. Khalatur

Protein-like copolymers: computer simulation

The notion of protein-like AB copolymers is introduced. Such copolymers can be generated with the help of the “instant image” of a dense homopolymer globule by assigning that the monomeric units closer to the globular surface are of A type, while the core is formed by the B type units. After that the primary structure of the chain is fixed, and one introduces different interaction potentials for A and B units. In doing so, we have in mind mainly aqueous systems and analogy with globular proteins, therefore A units are regarded as hydrophilic, and B units as hydrophobic. By means of Monte Carlo simulation using the bond fluctuation model we study the coil–globule transition for a protein-like copolymer upon the increase of attraction of hydrophobic B units, and compare the results with those for random AB copolymers. From the analysis of the primary structure of protein-like copolymers one can see that the “degree of blockiness” of the protein-like sequence is higher than for random copolymers, therefore the copolymers with the “random-block” primary structure are generated for comparison as well (the average length of A and B sequences being the same as for protein-like copolymers). It is shown that the coil–globule transition in protein-like copolymers occurs at higher temperatures, is more abrupt and has faster kinetics than for random copolymers with the same A/B composition and for random-block copolymers with the same A/B composition and “degree of blockiness”. The globules of protein-like copolymers exhibit a dense micelle-like core of hydrophobic B units stabilized by the long dangling loops of hydrophilic A units. Apparently, a protein-like copolymer “inherits” some of the properties of the “parent globule” which is reflected in the special long-range correlations in primary structure.

Peptide nanofibrils boost retroviral gene transfer and provide a rapid means for concentrating viruses

Inefficient gene transfer and low virion concentrations are common limitations of retroviral transduction. We and others have previously shown that peptides derived from human semen form amyloid fibrils that boost retroviral gene delivery by promoting virion attachment to the target cells. However, application of these natural fibril-forming peptides is limited by moderate efficiencies, the high costs of peptide synthesis, and variability in fibril size and formation kinetics. Here, we report the development of nanofibrils that self-assemble in aqueous solution from a 12-residue peptide, termed enhancing factor C (EF-C). These artificial nanofibrils enhance retroviral gene transfer substantially more efficiently than semen-derived fibrils or other transduction enhancers. Moreover, EF-C nanofibrils allow the concentration of retroviral vectors by conventional low-speed centrifugation, and are safe and effective, as assessed in an ex vivo gene transfer study. Our results show that EF-C fibrils comprise a highly versatile, convenient and broadly applicable nanomaterial that holds the potential to significantly facilitate retroviral gene transfer in basic research and clinical applications.

Structural organization of water-containing Nafion: The integral equation theory

Using the mutually consistent variant of the integral equation polymer reference interaction site model (RISM) theory and the chemically realistic rotational isomeric state (RIS) model, we perform a molecular level modeling of the specific structural organization of perfluorosulfonic acid ionomer (Nafion) with certain amount of physisorbed water. Our results establish molecular scale information necessary for understanding the equilibrium structure and thermodynamics of water-containing Nafion as well as water distribution and ionic (molecular) transport phenomena in hydrated Nafion membranes. As a first step in this direction, semi-empirical, quantum mechanical calculations on the molecular structures and energies of the polymeric backbone and pendant chains of Nafion with and without additional water molecules are carried out. These data are used in the single-polymer RIS Monte Carlo simulation, in which the short-range intramolecular interactions are taken into account via appropriate matrices of statistical weights. The local structure and morphology of the entire bicomponent water-containing system is calculated consistently on the basis of the RISm theory at different contents of absorbed water. We find that the addition of even a relatively small amount of water leads to the strong intensification of aggregation processes observed for polar sulfonic acid (SO 3 H) groups. Water molecules and polar SO 3 H groups form mixed aggregates with a three-layer structure. Incorporation of water molecules inside the aggregates results in an increase of their stability and leads to the increase of the number of associating groups in a stable aggregate. With increasing the number of incorporated solvent molecules, the average size of mixed aggregates increases. The results obtained in the present study support the concept of an irregularly shaped cluster surfaces. Such geometries are favorable to the formation of long channels of connected water-containing aggregates providing the unique permeability characteristics of Nafion membranes. In addition, we investigate the clustering and continuum percolation in the water phase, using the formalism of pairconnectedness correlation functions. The mean cluster size found theoretically is in reasonable agreement with the corresponding experimental estimates existing in the literature.

Primary sequences of proteinlike copolymers: Levy-flight–type long-range correlations

We consider the statistical properties of primary sequences of two-letter HP copolymers (H for hydrophobic and P for polar) designed to have water soluble globular conformations with H monomers shielded from water inside the shell of P monomers. We show, both by computer simulations and by exact analytical calculation, that for large globules and flexible polymers such sequences exhibit long-range correlations which can be described by Levy-flight statistics.

Molecular dynamics simulation study of adsorption of polymer chains with variable degree of rigidity. I. Static properties

The adsorption of a single polymer chain onto a solid surface is investigated by molecular dynamics simulations. The chain is composed of mass points interacting via a truncated Lennard‐Jones potential, i.e., the excluded volume interaction is taken into account, and grafted to the surface with one end. The average adsorption degree is calculated for various chain lengths (N = 16, 32, 64, 128) and adsorption energies. In addition, the scaling behavior of the adsorption degree and the radius of gyration is investigated. The adsorption degree and the average length of loops and tails are obtained for chains of various stiffnesses. In this context, we find that stiffer chains adsorb more easily. Moreover, the distribution of the mass points perpendicular to the surface as well as the orientation of the bonds with respect to the surface is discussed for various adsorption energies and stiffnesses.

Structural Organization of Water‐Containing Nafion: A Cellular‐Automaton‐Based Simulation

Using the cellular-automaton-based simulation technique, we study the processes of self-organization in the systems of comb-like copolymers with strongly attracting (end-functionalized) size-chains in the presence of low-molecular-weight water-like solvent. This molecular level modeling reflects the basic features of the specific structural organization of perfluorosulfonic acid ionomer (Nafion) with certain amount of physisprbed water, We compare the simulation data with the existing phenomenological models used in the literature to describe the structural features of water-swollen ionomer membranes and the results of our previous calculations based on the mutually consistent integral equation theory and the chemically realistic rotational isomeric state (RIS) model. Our attention is focused on the effect of water on the local aggregate structure, the shape of mixed, water-containing aggregates, and on system morphology.

Molecular dynamics study of the solution of semiflexible telechelic polymer chains with strongly associating end-groups

We present the results of molecular dynamics simulations of micelle organization as well as the formation of micellar aggregates in the solutions of semiflexible telechelic chains with strongly attracting end-groups (“sticker sites”). Using the cluster size distribution function, we study associative equilibrium in the system of flexible and semiflexible chains. It is found that this process corresponds to the so-called “open association” model for micelle formation. The critical temperature of micelle formation Tc is calculated as a function of chain rigidity and system density ρ. We find that the value of Tc increases monotonically with the increase of Kuhn segment length A. Such a behavior takes place in wide range of densities, but only if the value of ρ is somewhat smaller than some threshold value. At high density, we observe the opposite tendency; the temperature Tc decreases monotonically as the value of A is increased. The type of equilibrium microstructures, emerging as a result of micellization...

Self-assembling nanofibers from thiophene-peptide diblock oligomers: a combined experimental and computer simulations study.

We report herein the synthesis of a novel type of hybrid compound that consists of a poly(ethylene oxide) (PEO) functionalized β-sheet peptide sequence covalently linked to an alkylated quaterthiophene moiety. Compounds of this class are highly promising for technological applications because their self-assembly and stimuli-responsive behavior, which is mainly caused by the peptide moieties, combined with the potential semiconducting properties of oligothiophenes provides unprecedented opportunities for the design of advanced materials at the nanoscale in such areas as, for example, organic electronics and sensor design for chemical and biomedical applications. The compound presented herein is experimentally shown to form stable fibrillar aggregates that are visualized by both transmission electron and atomic force microscopy. We developed a theoretical methodology to study the possible intermolecular arrangements and their characteristic features with the help of all-atom MD simulations, while simultaneously incorporating available experimental data into the model. Large-scale atomistic simulations of several fibrillar aggregates with different molecular arrangements were performed. The results of the simulations are compared with experimental data, which leads to the proposition of a likely model for the arrangement of the individual molecules within the observed aggregates.

Aggregation and counterion condensation in solution of charged proteinlike copolymers: A molecular-dynamics study

We present the results of molecular dynamics simulations of charged proteinlike hydrophobic–hydrophilic (HP) copolymers with a fixed charge distribution under pure solvent conditions. The processes of coil-to-globule transition, aggregation of polymer globules, and counterion condensation are studied in detail as a function of temperature. Various static structure factors and pair correlation functions, that occur in polyelectrolyte solutions, are also analyzed. Our simulations show that the chains pass through strong conformational changes while changing temperature. We find three different temperature regimes which are characterized by a different behavior of Coulomb energy, chain sizes, and pair correlation functions. In the high-temperature regime, at the reduced temperature T>3.0, the chains have an extended conformation with many hydrophobic blobs. As temperature is decreased, one observes a counterion condensation and sharp decrease in chain size. In this regime, we observe a solution of nonaggrega...

Simulation of self-associating polymer systems. I. Shear-induced structural changes

We present the results of nonequilibrium molecular dynamics (NEMD) studies of self-associating polymer systems composed of flexible telechelic chains with associating end-groups (“stickers”). Formation of micellar aggregates, their structure and structural characteristics of associative polymer network (micellar gel) are studied under the influence of external shearing forces. When the association energy ec is quite large (ec⩾ec*, where ec* is a critical association energy corresponding to the gelation transition at rest), the spatial organization of the system as a whole is characterized by a typical network architecture with bridging chains connecting different micellar aggregates. The shearing forces cause only a slight perturbation in the structural properties of the sol (at ec<ec*). However, when the association energy ec becomes quite large (ec≳ec*), we observe sharp structural variations as the shear force is increased. At sufficiently strong attraction between stickers, the shear flow facilitates ...