Dendrimer Dynamics: A Review of Analytical Theories and Molecular Simulation Methods.

The theoretical study of dendrimers is reviewed, considering both analytical approaches and molecular simulation methods. We discuss the effect of molecular symmetry on the degeneracy of the relaxation times, and then the calculation of observable quantities, in particular the intrinsic viscosity, and then the viscoelastic complex modulus and the dynamic structure factor, in comparison with the available experimental data. In particular, the maximum intrinsic viscosity with increasing molar mass is analyzed in some detail.

Understanding Surface Interaction and Inclusion Complexes between Piroxicam and Native or Crosslinked β-Cyclodextrins: The Role of Drug Concentration.

Drug concentration plays an important role in the interaction with drug carriers affecting the kinetics of release process and toxicology effects. Cyclodextrins (CDs) can solubilize hydrophobic drugs in water enhancing their bioavailability. In this theoretical study based on molecular mechanics and molecular dynamics methods, the interactions between β-cyclodextrin and piroxicam, an important nonsteroidal anti-inflammatory drug, were investigated.

Hydrogen Bonding in a -Glutamine-Based Polyamidoamino Acid and its pH-Dependent Self-Ordered Coil Conformation.

This paper reports on synthesis, acid-base properties, and self-structuring in water of a chiral polyamidoamino acid, M--Gln, obtained from the polyaddition of -methylenebisacrylamide with -glutamine, with the potential of establishing hydrogen bonds through its -amide pendants. The M--Gln showed pH-responsive circular dichroism spectra, revealing ordered conformations. Structuring was nearly insensitive to ionic strength but sensitive to denaturing agents.

A Molecular Dynamics Study of a Photodynamic Sensitizer for Cancer Cells: Inclusion Complexes of γ-Cyclodextrins with C.

Photodynamic therapy is an emerging treatment of tumor diseases. The complexes with γ-cyclodextrins (γ-CD) and fullerenes or their derivatives can be used as photosensitizers by direct injection into cancer cells. Using molecular mechanics and molecular dynamics methods, the stability and the geometry of the 2:1 complexes [(γ-CD)/C] are investigated analyzing the differences with the analogous C complexes, studied in a previous theoretical work and experimentally found to be much less efficient in cancer therapy.

Self-Structuring in Water of Polyamidoamino Acids with Hydrophobic Side Chains Deriving from Natural α-Amino Acids.

This paper reports on synthesis, acid-base properties and self-structuring in water of chiral polyamidoamino acids (PAACs) obtained by polyaddition of ,'-methylenebisacrylamide with -alanine, -valine and -leucine (M--Ala, M--Val, M--Leu) with potential for selective interactions with biomolecules. The polymers maintained the acid-base properties of amino acids. In water, the circular dichroism spectra of PAACs revealed pH-dependent structuring in the range 3⁻11 and in the wavelength interval 200⁻280 nm.

Self-Ordering Secondary Structure of d- and l-Arginine-Derived Polyamidoamino Acids.

This paper reports on synthesis, acid-base properties and pH-dependent structuring in water of d-, l- and d,l-ARGO7, bioinspired polymers obtained by polyaddition of the corresponding arginine stereoisomers with ,'-methylenebis(acrylamide). The circular dichroism spectra of d- and l-ARGO7 showed a peak at 228 nm and quickly and reversibly responded to pH changes, but were nearly unaffected by temperature, ionic strength, and denaturating agents. Theoretical modeling studies of L-ARGO7 showed that it assumed a folded structure.

Inclusion complexes of β-cyclodextrin with tricyclic drugs: an X-ray diffraction, NMR and molecular dynamics study.

Tricyclic fused-ring cyclobenzaprine () and amitriptyline () form 1:1 inclusion complexes with β-cyclodextrin (β-CD) in the solid state and in water solution. Rotating frame NOE experiments (ROESY) showed the same geometry of inclusion for both /β-CD and /β-CD complexes, with the aromatic ring system entering the cavity from the large rim of the cyclodextrin and the alkylammonium chain protruding out of the cavity and facing the secondary OH rim. These features matched those found in the molecular dynamics (MD) simulations in solution and in the solid state from single-crystal X-ray diffraction of /β-CD and /β-CD complexes.

Aggregation behavior of amphiphilic cyclodextrins in a nonpolar solvent: evidence of large-scale structures by atomistic molecular dynamics simulations and solution studies.

Chemically modified cyclodextrins carrying both hydrophobic and hydrophilic substituents may form supramolecular aggregates or nanostructures of great interest. These systems have been usually investigated and characterized in water for their potential use as nanocarriers for drug delivery, but they can also aggregate in apolar solvents, as shown in the present paper through atomistic molecular dynamics simulations and dynamic light scattering measurements. The simulations, carried out with a large number of molecules in vacuo adopting an unbiased bottom-up approach, suggest the formation of bidimensional structures with characteristic length scales of the order of 10 nm, although some of these sizes are possibly affected by the assumed periodicity of the simulation cell, in particular at longer lengths.

Aggregation behaviour of amphiphilic cyclodextrins: the nucleation stage by atomistic molecular dynamics simulations.

Amphiphilically modified cyclodextrins may form various supramolecular aggregates. Here we report a theoretical study of the aggregation of a few amphiphilic cyclodextrins carrying hydrophobic thioalkyl groups and hydrophilic ethylene glycol moieties at opposite rims, focusing on the initial nucleation stage in an apolar solvent and in water. The study is based on atomistic molecular dynamics methods with a "bottom up" approach that can provide important information about the initial aggregates of few molecules.

Separation of chiral nanotubes with an opposite handedness by chiral oligopeptide adsorption: A molecular dynamics study.

The separation of enantiomeric chiral nanotubes that can form non-covalent complexes with an unlike stability upon adsorption of chiral molecules is a process of potential interest in different fields and applications. Using fully atomistic molecular dynamics simulations, we report in this paper a theoretical study of the adsorption and denaturation of an oligopeptide formed by 16 chiral amino acids having a helical structure in the native state on both the inner and the outer surface of the chiral (10, 20) and (20, 10) single-walled carbon nanotubes having an opposite handedness, and of the armchair (16, 16) nanotube with a similar diameter for comparison. In the final adsorbed state, the oligopeptide loses in all cases its native helical conformation, assuming elongated geometries that maximize its contact with the surface through all the 16 amino acids.

Atomistic simulation of hydrophobin HFBII conformation in aqueous and fluorous media and at the water/vacuum interface.

Hydrophobins are proteins of interest for numerous applications thanks to their unique conformational and surface properties and their ability to self-assemble at interfaces. Here we report fully atomistic molecular mechanics and molecular dynamics results together with circular dichroism experimental data, aimed to study the conformational properties of the hydrophobin HFBII in a fluorinated solvent in comparison with a water solution and/or at an aqueous/vacuum interface. Both the atomistic simulations and the circular dichroism data show the remarkable structural stability of HFBII at all scales in all these environments, with no significant structural change, although a small cavity is formed in the fluorinated solvent.

Surface topography effects in protein adsorption on nanostructured carbon allotropes.

We report a molecular dynamics (MD) simulation study of protein adsorption on the surface of nanosized carbon allotropes, namely single-walled carbon nanotubes (SWNT) considering both the convex outer surface and the concave inner surface, together with a graphene sheet for comparison. These systems are chosen to investigate the effect of the surface curvature on protein adsorption at the same surface chemistry, given by sp(2) carbon atoms in all cases. The simulations show that proteins do favorably interact with these hydrophobic surfaces, as previously found on graphite which has the same chemical nature.

Titanium oxide modeling and design for innovative biomedical surfaces: a concise review.

The natural oxide layer on implantable alloys insulates the reactive underlying metal from the physiological environment, preventing substrate corrosion and device failure. This type of oxide film has had a major role in the minimization of functional failure and toxic response after implantation in the first generation biomaterials. Recent advances in theoretical, computational, and experimental surface engineering tools provide the foundation for the design of novel devices with improved performances in this regard based on conventional implantable metal alloys.

Molecular modelling of protein adsorption on the surface of titanium dioxide polymorphs.

This paper reports a molecular modelling study of the adsorption of protein subdomains with unlike secondary structures on different surfaces of ceramic titanium dioxide (TiO(2)), forming a passivating film on titanium biomaterials that provides the interface between the bulk metal and the physiological environment, affecting its biocompatibility and performance. Using molecular dynamics methods, we study the effect of the nanoscale structure of the common TiO(2) polymorphs (rutile, anatase and brookite) on the adsorption of an albumin subdomain and on two connected fibronectin modules, respectively containing α-helices and β-sheets. We find that the larger protein subdomain shows a stronger adsorption, as expected because of its size, but also that the three surfaces behave differently.

Trends in biomedical engineering: focus on Smart Bio-Materials and Drug Delivery.

The present article reviews on different research lines, namely: drug and gene delivery, surface modification/modeling, design of advanced materials (shape memory polymers and biodegradable stents), presently developed at Politecnico di Milano, Italy. For gene delivery, non-viral polycationic-branched polyethylenimine (b-PEI) polyplexes are coated with pectin, an anionic polysaccharide, to enhance the polyplex stability and decrease b-PEI cytotoxicity. Perfluorinated materials, specifically perfluoroether, and perfluoro-polyether fluids are proposed as ultrasound contrast agents and smart agents for drug delivery.

Protein adsorption on biomaterial and nanomaterial surfaces: a molecular modeling approach to study non-covalent interactions.

Atomistic computer simulations of protein adsorption on the heterogeneous surface of biomaterials and nanomaterials are reviewed. First, we present a very brief introduction to some relevant issues concerning force fields and the computational methodologies currently used, in particular molecular dynamics simulations for studying non-covalent interactions in general. The main results are then discussed, considering the adsorption of different protein subdomains and of whole proteins on different surfaces of an unlike nature.

Modeling the adsorption behavior of linear end-functionalized poly(ethylene glycol) on an ionic substrate by a coarse-grained Monte Carlo approach.

The rheology of cement pastes can be controlled by polymeric dispersants such as branched polyelectrolytes that adsorb on the surfaces of silicate particles. In the present work, we analyze the adsorption behavior of ad hoc-prepared end-carboxylated poly(ethylene glycol), or PEG, on CaCO(3) particles as a model of cement in an early hydration stage. The experimental adsorption isotherms form the base of a theoretical study aimed at unraveling polymer conformational aspects of adsorption.

A molecular dynamics study of the inclusion complexes of C60 with some cyclodextrins.

The strongly hydrophobic C(60) fullerene is a carbon allotrope of huge interest in materials science and in pharmaceutical chemistry that can be solubilized in water either by extensive chemical functionalization or by inclusion in appropriate carriers such as the cyclodextrins with formation of host-guest complexes. Here we report a molecular dynamics study of the complexes formed in solution by C(60) with gamma- and delta-cyclodextrins. The most stable host-guest complex stoichiometry is determined to be 2:1 through simulations in vacuo and in explicit water by the stepwise addition of the cyclodextrins to C(60).

Protein adsorption on a hydrophobic surface: a molecular dynamics study of lysozyme on graphite.

Adsorption of human lysozyme on hydrophobic graphite is investigated through atomistic computer simulations with molecular mechanics (MM) and molecular dynamics (MD) techniques. The chosen strategy follows a simulation protocol proposed by the authors to model the initial and the final adsorption stage on a bare surface. Adopting an implicit solvent and considering 10 starting molecular orientations so that all the main sides of the protein can face the surface, we first carry out an energy minimization to investigate the initial adsorption stage, and then long MD runs of selected arrangements to follow the surface spreading of the protein maximizing its adsorption strength.

Validating a strategy for molecular dynamics simulations of cyclodextrin inclusion complexes through single-crystal X-ray and NMR experimental data: a case study.

A theoretical and experimental study about the formation and structure of the inclusion complex (-)-menthyl-O-beta-D-glucopyranoside 1 with beta-cyclodextrin (beta-CD) 2 is presented as paradigmatic case study to test the results of molecular dynamics (MD) simulations. The customary methodological approach-the use of experimental geometrical parameters as restraints for MD runs-is logically reversed and the calculated structures are a posteriori compared with those obtained from NMR spectroscopy in D(2)O solution and single crystal X-ray diffraction so as to validate the simulation procedure. The guest molecule 1 allows for a broad repertoire of intermolecular interactions (dipolar, hydrophobic, hydrogen bonds) concurring to stabilize the host-guest complex, thus providing the general applicability of the simulation procedure to cyclodextrin physical chemistry.

Surface hydration of polymeric (bio)materials: a molecular dynamics simulation study.

The surface hydration of some crystalline polymeric (bio)materials is investigated at room temperature using molecular mechanics and molecular dynamics techniques through the statistical distribution of the water molecules as a function of their distance from the surface atoms. Considering different crystalline polymers such as polyethylene, poly(vinylidene fluoride), and poly(m-phenylene isophthalamide), and in particular their different crystal faces, we can take into account unlike surface chemistries and their subnanoscale topologies. Such features are ultimately related to the intermolecular forces between the exposed groups of the specific crystal face and the water molecules, and those among the polymer chains, which also affects the thermal motion of the surface repeat units.

Understanding the performance of biomaterials through molecular modeling: crossing the bridge between their intrinsic properties and the surface adsorption of proteins.

Molecular modeling and computer simulations can yield significant new insight at the atomistic level about the performance of biomaterials in a biological environment. In this paper, we review our approach to a consistent theoretical picture of the bulk and surface properties of biomaterials. The predicted properties do encompass in particular the mechanical behavior and the surface hydration of these materials, and the surface physisorption of proteins, or polypeptides in general.

Sequential adsorption of proteins and the surface modification of biomaterials: a molecular dynamics study.

The sequential adsorption of two proteins of the same or of an unlike nature on a heterogeneous hydrophobic surface is investigated through atomistic molecular dynamics simulations. By modeling two real protein fragments having a different secondary structure (alpha-helices or beta-sheets) on a graphite surface, the pre-adsorbed polypeptides are shown to modify the hydropathy of this substrate. Therefore, the graphite surface modified by the first adsorbed protein becomes more similar to a hydrophilic one in terms of both the interaction energy and the size of the second protein after the possible surface spreading.

Protein adsorption on the hydrophilic surface of a glassy polymer: a computer simulation study.

Using atomistic computer simulations, we study the adsorption of different globular protein fragments with different secondary structures on the surface of a hydrophilic glassy polymer, poly(vinyl alcohol), or PVA, and compare the results with our earlier calculations on hydrophobic graphite. The simulations were mainly carried out with implicit solvent in an effective dielectric medium by energy minimizations and molecular dynamics at room temperature. We find that on the hydrophilic PVA surface the fragments basically retain their globular shape with an incomplete denaturation, at variance with our earlier results for the same fragments on graphite.

Computer simulation of bulk mechanical properties and surface hydration of biomaterials.

Some intrinsic properties of biomaterials are calculated with atomistic computer simulations through energy minimizations and molecular dynamics methods. The mechanical properties of bulk polymers such as poly(vinyl alcohol) and poly(ethylene terephthalate) are obtained in terms of the Young's modulus, the bulk and shear moduli, and the Poisson ratio below the glass transition temperature. The calculated values apply to an ideal, defect-free sample, and therefore, they correspond to the theoretical upper limit for the mechanical behavior of these materials.