Computer simulations on oxidative stress-induced reactions in SARS-CoV-2 spike glycoprotein: a multi-scale approach.

Oxidative stress, which occurs when an organism is exposed to an adverse stimulus that results in a misbalance of antioxidant and pro-oxidants species, is the common denominator of diseases considered as a risk factor for SARS-CoV-2 lethality. Indeed, reactive oxygen species caused by oxidative stress have been related to many virus pathogenicity. In this work, simulations have been performed on the receptor binding domain of SARS-CoV-2 spike glycoprotein to study what residues are more susceptible to be attacked by ·OH, which is one of the most reactive radicals associated to oxidative stress. The results indicate that isoleucine (ILE) probably plays a crucial role in modification processes driven by radicals. Accordingly, QM/MM-MD simulations have been conducted to study both the ·OH-mediated hydrogen abstraction of ILE residues and the induced modification of the resulting ILE radical through hydroxylation or nitrosylation reactions. All in all, in silico studies show the importance of the chemical environment triggered by oxidative stress on the modifications of the virus, which is expected to help for foreseeing the identification or development of antioxidants as therapeutic drugs.

Unravelling the molecular interactions between the SARS-CoV-2 RBD spike protein and various specific monoclonal antibodies.

Vaccination against SARS-CoV-2 just started in most of the countries. However, the development of specific vaccines against SARS-CoV-2 is not the only approach to control the virus and monoclonal antibodies (mAbs) start to merit special attention as a therapeutic option to treat COVID-19 disease. Here, the main conformations and interactions between the receptor-binding domain (RBD) of spike glycoprotein of SARS-CoV-2 (S protein) with two mAbs (CR3022 and S309) and the ACE2 cell receptor are studied as the main representatives of three different epitopes on the RBD of S protein. The combined approach of 1 µs accelerated molecular dynamics (aMD) and ab-initio hybrid molecular dynamics is used to identify the most predominant interactions under physiological conditions. Results allow to determine the main receptor-binding mapping, hydrogen bonding network and salt bridges in the most populated antigen-antibody interface conformations. The deep knowledge on the protein-protein interactions involving mAbs and ACE2 receptor with the spike glycoprotein of SARS-CoV-2 increases background knowledge to speed up the development of new vaccines and therapeutic drugs.

In silico antibody engineering for SARS-CoV-2 detection.

Engineered immunoglobulin-G molecules (IgGs) are of wide interest for the development of detection elements in protein-based biosensors with clinical applications. The strategy usually employed for the de novo design of such engineered IgGs consists on merging fragments of the three-dimensional structure of a native IgG, which is immobilized on the biosensor surface, and of an antibody with an exquisite target specificity and affinity. In this work conventional and accelerated classical molecular dynamics (cMD and aMD, respectively) simulations have been used to propose two IgG-like antibodies for COVID-19 detection. More specifically, the crystal structure of the IgG1 B12 antibody, which inactivates the human immunodeficiency virus-1, has been merged with the structure of the antibody CR3022 Fab tightly bounded to SARS-CoV-2 receptor-binding domain (RBD) and the structure of the S309 antibody Fab fragment complexed with SARS-CoV-2 RBD. The two constructed antibodies, named IgG1-CR3022 and IgG1-S309, respectively, have been immobilized on a stable gold surface through a linker. Analyses of the influence of both the merging strategy and the substrate on the stability of the two constructs indicate that the IgG1-S309 antibody better preserves the neutralizing structure than the IgG1-CR3022 one. Overall, results indicate that the IgG1-S309 is appropriated for the generation of antibody based sensors for COVID-19 diagnosis.

Temperature effect on the SARS-CoV-2: A molecular dynamics study of the spike homotrimeric glycoprotein.

Rapid spread of SARS-CoV-2 virus have boosted the need of knowledge about inactivation mechanisms to minimize the impact of COVID-19 pandemic. Recent studies have shown that SARS-CoV-2 virus can be disabled by heating, the exposure time for total inactivation depending on the reached temperature (e.g. more than 45 min at 329 K or less than 5 min at 373 K. In spite of recent crystallographic structures, little is known about the molecular changes induced by the temperature. Here, we unravel the molecular basis of the effect of the temperature over the SARS-CoV-2 spike glycoprotein, which is a homotrimer with three identical monomers, by executing atomistic molecular dynamics (MD) simulations at 298, 310, 324, 338, 358 and 373 K. Furthermore, both the closed down and open up conformational states, which affect the accessibility of receptor binding domain, have been considered. Our results suggest that the spike homotrimer undergoes drastic changes in the topology of the hydrogen bonding interactions and important changes on the secondary structure of the receptor binding domain (RBD), while electrostatic interactions (i.e. salt bridges) are mainly preserved. The proposed inactivation mechanism has important implications for engineering new approaches to fight the SARS-CoV-2 coronavirus, as for example, cleaving or reorganizing the hydrogen bonds through chaotropic agents or nanoparticles with local surface resonant plasmon effect.

Main-chain scission of individual macromolecules induced by solvent swelling.

We present a comprehensive investigation of main-chain scission processes affecting peripherally charged and neutral members of a class of dendronized polymers (DPs) studied in our laboratory. In these thick, sterically highly congested macromolecules, scission occurs by exposure to solvents, in some cases at room temperature, in others requiring modest heating. Our investigations rely on gel permeation chromatography and atomic force microscopy and are supported by molecular dynamics simulations as well as by electron paramagnetic resonance spectroscopy. Strikingly, DP main-chain scission depends strongly on two factors: first the solvent, which must be highly polar to induce scission of the DPs, and second the dendritic generation g. In DPs of generations 1 ≤ g ≤ 8, scission occurs readily only for g = 5, no matter whether the polymer is charged or neutral. Much more forcing conditions are required to induce degradation in DPs of g ≠ 5. We propose solvent swelling as the cause for the main-chain scission in these individual polymer molecules, explaining in particular the strong dependence on g: g < 5 DPs resemble classical polymers and are accessible to the strongly interacting, polar solvents, whereas g > 5 DPs are essentially closed off to solvent due to their more closely colloidal character. g = 5 DPs mark the transition between these two regimes, bearing strongly sterically congested side chains which are still solvent accessible to some degree. Our results suggest that, even in the absence of structural elements which favour scission such as cross-links, solvent swelling may be a generally applicable mechanochemical trigger. This may be relevant not only for DPs, but also for other types of sterically strongly congested macromolecules.

Isomeric cationic ionenes as n-dopant agents of poly(3,4-ethylenedioxythiophene) for in situ gelation.

Three isomeric ionene polymers containing 1,4-diazabicyclo[2.2.2]octane (DABCO) and N,N'-(x-phenylene)dibenzamide (x = ortho-/meta-/para-) linkages have been used as dopant agents to produce n-doped poly(3,4-ethylenedioxythiophene) (PEDOT) electrodes by reducing already dedoped conducting polymer (CP) films. This work focuses on the influence of the ionene topology on both the properties of n-doped PEDOT:ionene electrodes and the success of the in situ thermal gelation of the ionene inside the CP matrix. The highest doping level is reached for the para-isomeric ionene-containing electrode, even though the content of ortho- and meta-topomers in the corresponding n-doped PEDOT:ionene electrodes is greater. Thus, many of the incorporated ionene units are not directly interacting with CP chains and, therefore, they do not play an active role as n-dopant agents but they are crucial for the in situ formation of the ionene hydrogels. The effect of the ionene topology is practically non-existent on properties such as the specific capacitance and wettability of PEDOT:ionene films, and it is small but non-negligible on the electrochemical and thermal stability. In contrast, the surface morphology, topography, and distribution of dopant molecules significantly depend on the ionene topology. In situ thermal gelation was successful in PEDOT films n-doped with the ortho- and para-topomers, even though this assembly process was much faster for the former than for the latter. The gelation considerably improved the mechanical response of the electropolymerized PEDOT film, which was practically non-existent before it. Molecular dynamics simulations prove that the strength and abundance of PEDOTionene specific interactions (i.e. π-π stacking, N-HS hydrogen bonds and both N+O and N+S interactions) are higher for the meta-isomeric ionene, for which the in situ gelation was not achieved, than for the ortho- and para-ones.

Cationic ionene as an n-dopant agent of poly(3,4-ethylenedioxythiophene).

We report the reduction of poly(3,4-ethylenedioxythiophene) (PEDOT) films with a cationic 1,4-diazabicyclo[2.2.2]octane-based ionene bearing N,N'-(meta-phenylene)dibenzamide linkages (mPI). Our main goal is to obtain n-doped PEDOT using a polymeric dopant agent rather than small conventional tetramethylammonium (TMA), as is usual. This has been achieved using a three-step process, which has been individually optimized: (1) preparation of p-doped (oxidized) PEDOT at a constant potential of +1.40 V in acetonitrile with LiClO4 as the electrolyte; (2) dedoping of oxidized PEDOT using a fixed potential of -1.30 V in water; and (3) redoping of dedoped PEDOT applying a reduction potential of -1.10 V in water with mPI. The resulting films display the globular appearance typically observed for PEDOT, with mPI being structured in separated phases forming nanospheres or ultrathin sheets. This organization, which has been supported by atomistic molecular dynamics simulations, resembles the nanosegregated phase distribution observed for PEDOT p-doped with poly(styrenesulfonate). Furthermore, the doping level achieved using mPI as the doping agent is comparable to that achieved using TMA, even though ionene provides distinctive properties to the conducting polymer. For example, films redoped with mPI exhibit much more hydrophilicity than the oxidized ones, whereas films redoped with TMA are hydrophobic. Similarly, films redoped with mPI exhibit the highest thermal stability, while those redoped with TMA show thermal stability that is intermediate between those of the latter and the dedoped PEDOT. Overall, the incorporation of an mPI polycation as the n-dopant into PEDOT has important advantages for modulating the properties of this emblematic conducting polymer.

Hydroxyapatite with Permanent Electrical Polarization: Preparation, Characterization, and Response against Inorganic Adsorbates.

Permanently polarized hydroxyapatite (HAp) particles have been prepared by applying a constant DC of 500 V at 1000 °C for 1 h to the sintered mineral. This process causes important chemical changes, as the formation of OH- defects (vacancies), the disappearance of hydrogenophosphate ions at the mineral surface layer, and structural variations reflected by the increment of the crystallinity. As a consequence, the electrochemical properties and electrical conductivity of the polarized mineral increase noticeably compared with as-prepared and sintered samples. Moreover, these increments remain practically unaltered after several months. In addition, permanent polarization favours significantly the ability of HAp to adsorb inorganic bioadsorbates in comparison with as-prepared and sintered samples. The adsorbates cause a significant increment of the electrochemical stability and electrical conductivity with respect to bare polarized HAp, which may have many implications for biomedical applications of permanently polarized HAp.

Aromatic ionene topology and counterion-tuned gelation of acidic aqueous solutions.

Unusual gelation of acidic solutions was achieved using polycations bearing quaternary ammonium moieties. These ionene polymers are based on a disubstituted phenylene dibenzamide core, which allows the construction of different topomers (i.e. ortho-1, meta-2 and para-3). The topology of the polymers was found to play a key role on their aggregation behaviour both in pure water and in a variety of aqueous acidic solutions leading to the formation of stable acidic gels. Specifically, ortho-1 showed superior gelation ability than the analogues meta-2 and para-3 in numerous solutions of different pH and ionic strengths. Lower critical gelation concentrations, higher gel-to-sol transition temperatures and faster gelation were usually observed for ortho-1 regardless the solvent system. Detailed computational molecular dynamic simulations revealed a major role of the counterion (Cl-) and specific polymerpolymer interactions. In particular, hydrogen bonds, N-Hπ interactions and intramolecular π-π stacking networks are distinctive in ortho-1. In addition, counterions located at internal hydration regions also affect to such polymerpolymer interactions, acting as binders and, therefore, providing additional stability.

Dissolving Hydroxyolite: A DNA Molecule into Its Hydroxyapatite Mold.

In spite of the clinical importance of hydroxyapatite (HAp), the mechanism that controls its dissolution in acidic environments remains unclear. Knowledge of such a process is highly desirable to provide better understanding of different pathologies, as for example osteoporosis, and of the HAp potential as vehicle for gene delivery to replace damaged DNA. In this work, the mechanism of dissolution in acid conditions of HAp nanoparticles encapsulating double-stranded DNA has been investigated at the atomistic level using computer simulations. For this purpose, four consecutive (multi-step) molecular dynamics simulations, involving different temperatures and proton transfer processes, have been carried out. Results are consistent with a polynuclear decalcification mechanism in which proton transfer processes, from the surface to the internal regions of the particle, play a crucial role. In addition, the DNA remains protected by the mineral mold and transferred proton from both temperature and chemicals. These results, which indicate that biomineralization imparts very effective protection to DNA, also have important implications in other biomedical fields, as for example in the design of artificial bones or in the fight against osteoporosis by promoting the fixation of Ca(2+) ions.

Solvatochromism of dye-labeled dendronized polymers of generation numbers 1-4: comparison to dendrimers.

Two series of dendronized polymers (DPs) of generations g = 1-4 with different levels of dendritic substitution (low and high) and a solvatochromic probe at g = 1 level are used to study their swelling behavior in a collection of solvents largely differing in polarity as indicated by the Kamlet-Taft parameters. This is done by measuring the UV-Vis spectra of all samples in all solvents and determining the longest wavelength absorptions (λmax). The λmax values fall into a range defined by the extreme situations, when the solvatochromic probe is either fully surrounded by solvent or completely shielded against it. The former situation is achieved in a model compound and the latter situation is believed to be reached when in a poor solvent the dendritic shell around the backbone is fully collapsed. We observe that solvent penetration into the interior of the DPs decreases with increasing g and does so faster for the more highly dendritically substituted series than for the less highly substituted one. Interestingly, the swelling of the more highly substituted DP series already at the g = 4 level has decreased to approximately 20% of that at the g = 1 level which supports an earlier proposal that high g DPs can be viewed as nano-sized molecular objects. Furthermore, when comparing these two DP series with a g = 1-6 series of dendrimers investigated by Fréchet et al. it becomes evident that even the less substituted series of DPs is much less responsive to solvent changes as assessed by the solvatochromic probe than the dendrimers, suggesting the branches around the (polymeric) core in DPs to be more densely packed compared to those in dendrimers, thus, establishing a key difference between these two dendritic macromolecules.

Surviving Mass Extinctions through Biomineralized DNA.

Even in the worst of conditions, such as those which occurred during mass extinction events, life on Earth never totally stopped. Aggressive chemical and physical attacks able to sterilize or poison living organisms occurred repeatedly. Surprisingly, DNA was not degraded, denatured or modified to the point of losing the capability of transferring the genetic information to the next generations. After the events of mass extinction life was able to survive and thrive. DNA was passed on despite being an extremely fragile biomolecule. The potential implications of hydroxyapatite protection of DNA are discussed in this Concept article including how DNA acts as a template for hydroxyapatite (HAp) formation, how cell death can trigger biomineralization, and how DNA can be successfully released from HAp when the conditions are favorable for life.

An experimental-computer modeling study of inorganic phosphates surface adsorption on hydroxyapatite particles.

The adsorption of orthophosphate, pyrophosphate, triphosphate and a trisphosphonate onto hydroxyapatite has been examined using experiments and quantum mechanical calculations. Adsorption studies with FTIR and X-ray photoelectron spectroscopies have been performed considering both crystalline hydroxyapatite (HAp) and amorphous calcium phosphate particles, which were specifically prepared and characterized for this purpose. Density functional theory (DFT) calculations have been carried out considering the (100) and (001) surfaces of HAp, which were represented using 1 × 2 × 2 and 3 × 3 × 1 slab models, respectively. The adsorption of phosphate onto the two crystallographic surfaces is very much favored from an energetic point of view, which is fully consistent with current interpretations of the HAp growing process. The structures calculated for the adsorption of pyrophosphate and triphosphate evidence that this process is easier for the latter than for the former. Thus, the adsorption of pyrophosphate is severely limited by the surface geometry while the flexibility of triphosphate allows transforming repulsive electrostatic interactions into molecular strain. On the other hand, calculations predict that the trisphosphonate only adsorbs onto the (001) surface of HAp. Theoretical predictions are fully consistent with experimental data. Thus, comparison of DFT results and spectroscopic data suggests that the experimental conditions used to prepare HAp particles promote the predominance of the (100) surface. Accordingly, experimental identification of the adsorption of trisphosphonate onto such crystalline particles is unclear while the adsorption of pyrophosphate and triphosphate is clearly observed.

Synergistic approach to elucidate the incorporation of magnesium ions into hydroxyapatite.

Although the content of Mg(2+) in hard tissues is very low (typically ≤1.5 wt %), its incorporation into synthetic hydroxyapatite (HAp) particles and its role in the mineral's properties are still subject of intensive debate. A combined experimental-computational approach is used to answer many of the open questions. Mg(2+) -enriched HAp particles are prepared using different synthetic approaches and considering different concentrations of Mg(2+) in the reaction medium. The composition, morphology and structure of the resulting particles are investigated using X-ray photoelectron spectroscopy, energy dispersive X-ray spectroscopy, scanning and transmission electron microscopies, FTIR, and wide-angle X-ray diffraction. After this scrutiny, the role of the Mg(2+) in the first nucleation stages, before HAp formation, is investigated using atomistic molecular dynamics simulations. Saturated solutions are simulated with and without the presence of DNA, which has been recently used as a soft template in the biomineralization process. This synergistic investigation provides a complete picture of how Mg(2+) ions affect the mineralization from the first stages onwards.

Internal organization of macromonomers and dendronized polymers based on thiophene dendrons.

The internal organization of macromonomers (MGs) consisting of all-thiophene dendrons of generation g = 2 and 3 attached to a phenyl core, as well as of the dendronized polymers resulting from polymerization of these macromonomers (PG2 and PG3, respectively), has been investigated using theoretical methods. The conformational preferences of the MGs, determined using density functional theory calculations, are characterized by the relative orientation between dendrons and core. We find that the strain of the MGs increases with the generation number and is alleviated by small conformational re-arrangements of the peripheral thiophene rings. The conformations obtained for the MGs have subsequently been used to construct models for the dendronized polymers. Classical molecular dynamics simulations have evidenced that the interpenetration of dendrons belonging to different repeat units is very small for PG2. In contrast, the degree of interpenetration is found to be very high for PG3, which also shows a significant degree of backfolding (i.e. occurrence of peripheral methyl groups approaching the backbone). Consequently, PG2 behaves as a conventional linear flexible polymer bearing bulk pendant groups, whereas PG3 is better characterized as a semirigid homogeneous cylinder. The two polymers are stabilized by π-π stacking interactions, even though these are significantly more abundant for PG3 than for PG2; the average numbers of interactions per repeat unit are 3.0 and 8.8 for PG2 and PG3, respectively. While in these interactions the thiophene rings can adopt either parallel (sandwich) or perpendicular (T-shaped) dispositions, the former scenario turns out to be the most abundant.

Interactions in dendronized polymers: intramolecular dominates intermolecular.

In an attempt to relate atomistic information to the rheological response of a large dendritic object, interand intramolecular hydrogen bonds and p,p-interactions have been characterized in a dendronized polymer (DP) that consists of a polymethylmethacrylate backbone with tree-like branches of generation four (PG4) and contains both amide and aromatic groups. Extensive atomistic molecular dynamics simulations have been carried out on (i) an isolated PG4 chain and (ii) ten dimers formed by two PG4 chains associated with different degrees of interpenetration. Results indicate that the amount of nitrogen atoms involved in hydrogen bonding is ~11% while ~15% of aromatic groups participate in p,pinteractions. Furthermore, in both cases intramolecular interactions clearly dominate over intermolecular ones, while exhibiting markedly different behaviors. Specifically, the amount of intramolecular hydrogen bonds increases when the interpenetration of the two chains decreases, whereas intramolecular p,pinteractions remain practically insensitive to the amount of interpenetration. In contrast, the strength of the corresponding two types of intermolecular interactions decreases with interpenetration. Although the influence of complexation on the density and cross-sectional radius is relatively small, interpenetration affects significantly the molecular length of the DP. These results support the idea of treating DPs as long colloidal molecules.

Mineralization of DNA into nanoparticles of hydroxyapatite.

Encapsulation of DNA into hydroxyapatite (HAp) has been investigated using a rational approach that involves computer simulation and experimental techniques. The temporal evolution of the radial distribution functions derived from atomistic molecular dynamics simulations of Ca(2+), PO4(3-) and OH(-)-containing aqueous solutions in the presence and absence of B-DNA has been used to conclude that the backbone of the double helix acts as a template for HAp growth. More specifically, results reveal the formation of calcium phosphate clusters at the first stages of the simulations, which subsequently re-organize to nucleate HAp. This effect is produced in the absence and, especially, presence, of DNA indicating that the biomolecules do not inhibit but even promote mineral growth. Furthermore, computer simulations suggest that the diffusion of the OH(-) anions through the inorganic solution is the limiting step for the nucleation of the biomineral. Nanocapsules and crystalline nanorods of HAp containing DNA molecules inside have been prepared by mixing solutions containing Ca(2+) and PO4(3-) ions with fish sperm DNA at high pH. The dimensions and morphology of such nanostructures have been examined by transmission electron microscopy, while the characterization of the biomineral has been focused on the identification of DNA inside HAp using infrared, X-ray photoelectron and UV-vis spectroscopies, as well as gel electrophoresis. The biominerals reported in this work are important for biomedical applications requiring the protection of DNA from aggressive environmental conditions.

DNA adsorbed on hydroxyapatite surfaces.

Hydroxyapatite (HAp) particles with very different surface charges and compositions (i.e. different Ca/P and CO3 2-/PO4 3- ratios) have been obtained by varying the experimental conditions used during the chemical precipitation process. The DNA adsorption capacity and protection imparted against the attack of nucleases of HAp particles have been proved to depend on the surface charge while the buffering capacity is affected by the chemical composition. On the basis of both the surface charge and the crystallinity, the predominant planes at the surfaces of HAp particles have been identified. Atomistic molecular dynamics simulations of surfaces constructed with these planes (i.e. (001) and the two terminations of (010)) with the adsorbed B-DNA double helix have been performed to get microscopic understanding of the influence of the mineral in the biomolecule structure and the interaction energies. The results indicate that the DNA secondary structure is perfectly preserved on the (001) surface, this stability being accompanied by an attractive binding energy. In contrast, the (010) surface with PO4 3-, OH- and Ca2+ ions in the termination induces significant local and global deformations in the double helix, repulsive OH-(HAp)PO4 3- (DNA) interactions provoking the desorption of the biomolecule. Finally, although the termination of the (010) surface with PO4 3- and Ca2+ ions also deforms the double helix, it forms very strong attractive interactions with the biomolecule. These binding characteristics are in excellent agreement with the DNA adsorption and protection abilities experimentally determined for the HAp samples. Finally, the surface charge has been found less decisive than the chemical composition in the efficacy of the transfection process.

Computer simulation of fifth generation dendronized polymers: impact of charge on internal organization.

The internal organization of a fifth-generation dendronized polymer (PG5) has been investigated by atomistic molecular dynamics simulations in a vacuum. This study reveals an exceptional behavior of PG5 within the homologous series of g-generation PGg polymers. Three molecular configurations, which present a heterogeneous distribution of dendrons and an amount of backfolding lower than PG4 and PG6, have been obtained for PG5. The highest stability and closest agreement with available experimental data corresponds to a helical conformation characterized by a pitch of about 30 Å, thickness of 105 Å, and average density of 0.861 g/cm(3). While small angle neutron scattering studies of PG5 in solution show a constant radial density distribution around the backbone, we here in our vacuum studies find a cylindrical volume element of sharply reduced density reminiscent of a pore. This neutral PG5 was compared with its charged deprotected analogue, dePG5 in water, to see in as much the positive charges in the periphery of this macromolecule would affect its conformational behavior. During deprotection of PG5, the tert-butyloxycarbonyl protected amine groups are converted into ammonium, mimicking the experimental situation during a divergent synthesis procedure. The repulsive interactions among the positively charged ammonium groups are responsible for a huge (~30%) reduction of the average density and a small (~1%) increase of elongation of the helical backbone, which results in a structure with a spongy appearance. Also here, we find a reduced dendron density near the backbone which is compensated for by the pore being filled with water.

Atomistic organization and characterization of tube-like assemblies comprising peptide-polymer conjugates: computer simulation studies.

The structure and stability of the nanotube obtained by assembling peptide-polymer conjugates consisting of two poly(n-butyl acrylate) blocks coupled to the cyclic (D-alt-L)-octapeptide cyc[(L-Gln-D-Ala-L-Lys-D-Ala)2], have been investigated at the molecular level using atomistic molecular dynamics simulations. The effect of the wrapping polymer shells in the tube-like core, which consists of stacked beta-sheet cyclopeptides, has been examined by simulating assemblies of both unsubstituted cyclopeptides, and conjugates in chloroform and N,N-dimethylformamide solutions. Furthermore, the influence of the environment has been investigated by comparing conjugate assemblies in solution with those deposited on mica. In addition, nanotubes stabilized by beta-sheet-like hydrogen bonds between both parallel and antiparallel oriented cyclopeptides have been considered in all cases. The results, which have been analysed in terms of energy contributions, partial radial distribution functions, inter-subunit distances, shape of the cyclopeptide ring, internal van der Waals diameters, and both height and width of the nanostructures deposited on mica, have provided important microscopic insights. For example, analysis of both the energy terms and the structural dynamics obtained for the different assemblies indicate that the mica surface interacts more favourably with the parallel assembly than with the antiparallel ones, whereas the only configuration that is structurally stable in solution is the latter. Furthermore, adsorption onto the solid substrate produces a small deformation of the cylindrical molecular system.