Simulación de estructuras y propiedades de poliamidas helicoidales

Los objetivos que se persiguen la memoria presentada puede desglosarse en dos grandes bloques temáticos, los cuales están estrechamente relacionados.1) El estudio conformacional y estructural de diferentes poliamidas helicoidales con potencial interés industrial. Concretamente se ha abordado el estudio de los siguientes polímeros:- El ácido poli(-glutámico)- El ácido poli(-glutámico)- Complejos polipéptido - tensioactivo.- El poli(-benzil--glutamato)- Algunos poli(-alquil--glutamato)s- Algunos poli(-alquil--L-aspartato)s2) La predicción de la solubilidad de gases en polímeros cristalinos a partir del conocimiento de su estructura cristalina. Este último objetivo requiere el desarrollo de nuevas metodologías teóricas que permitan abordar el estudio de dicha solubilidad en fases altamente ordenadas Para llevar a cabo el estudio de la microestructa de los polímeros expuestos se han utilizado un gran número de métodos de simulación computacional, en función del tipo de propiedad física que se quisiera caracterizar.- Métodos Mecánocuánticos: Este tipo de metodologías ha sido utilizado para caracterizar las interacciones que determinan las preferencias conformacionales del ácido poli(-glutámico) y del ácido poli(-glutámico), así como, las interacciones que determinan la formación de los complejos polipéptido - tensioactivo.- Métodos basados en la Mecánica Molecular: Dentro de los diferentes métodos basados en este formalismo se han utilizado las metodologías siguientes:- Cálculo de la energía del empaquetamiento cristalino: Esta estrategia se ha utilizado para determinar las estructuras expuestas en la memoria.- Dinámica Molecular: Esta metodología se ha usado para la caracterización conformacional del ácido poli(-glutámico) y de los complejos polipéptido - tensioactivo.- Monte Carlo: Esta estrategia ha servido para estudiar las estructuras bifásicas características de algunos polímeros tipo peine, así como, como punto de partida para la predicción de la solubilidad de gases en polímeros cristalinos.Los resultados obtenidos en la memoria presentada han permitido caracterizar completamente diferentes familias de polímeros de origen natural potencialmente biodegradables. Este punto es de especial interés puesto que permite seguir avanzado en la obtención de materiales compatibles con el medio ambiente y con un coste razonable.A su vez, la posibilidad de poder predecir con un alto grado de precisión la solubilidad de gases en polímeros, nos permite presagiar el diseño de polímeros permeoselectivos, lo cual implica poder desarrollar materias primas para el desarrollo de productos industriales de altas prestaciones.Postprint (published version

Solvent effects on the properties of hyperbranched polythiophenes

The structural and electronic properties of all-thiophene dendrimers and dendrons in solution have been evaluated using very different theoretical approaches based on quantum mechanical (QM) and hybrid QM/molecular mechanics (MM) methodologies: (i) calculations on minimum energy conformations using an implicit solvation model in combination with density functional theory (DFT) or time-dependent DFT (TD-DFT) methods; (ii) hybrid QM/MM calculations, in which the solute and solvent molecules are represented at the DFT level as point charges, respectively, on snapshots extracted from classical molecular dynamics (MD) simulations using explicit solvent molecules, and (iii) QM/MM-MD trajectories in which the solute is described at the DFT or TD-DFT level and the explicit solvent molecules are represented using classical force-fields. Calculations have been performed in dichloromethane, tetrahydrofuran and dimethylformamide. A comparison of the results obtained using the different approaches with the available experimental data indicates that the incorporation of effects associated with both the conformational dynamics of the dendrimer and the explicit solvent molecules is strictly necessary to satisfactorily reproduce the properties of the investigated systems. Accordingly, QM/MM-MD simulations are able to capture such effects providing a reliable description of electronic properties–conformational flexibility relationships in all-Th dendrimers.Peer ReviewedPostprint (author's final draft

DNA - Conducting polymer complexes: A computational study of the hydrogen bond between building blocks

Ab initio quantum mechanical calculations at the MP2 level were used for an extensive study concerning the stability of hydrogen-bonded complexes formed by pyrrole and thiophene, which are the most common building blocks of conducting polymers, and DNA bases. Results indicated that very stable complexes were formed with pyrrole, which shows a clear tendency to form specific hydrogen-bonding interactions with nucleic acid bases. Furthermore, the strength of such interactions depends significantly on the base, growing in the following order: thymine < adenine ˜ cytosine < guanine. On the contrary, thiophene formed complexes stabilized by nonspecific interactions between the p-cloud of the ring and the N-H groups of the nucleic acid bases rather than specific hydrogen bonds. Overall, these results are fully consistent with experimental observations: polypyrrole is able not only to stabilize adducts with DNA but also to interact specifically, while the interactions of the latter with polythiophene and their derivatives are weaker and nonspecific. © 2008 American Chemical Society.Peer ReviewedPostprint (author's final draft

Introduction to molecular modeling of materials in an undergraduate engineering degree

Molecular modeling is a chemistry tool that has been widely used in the last decades to mainly support the basic concepts of general chemistry and organic chemistry, in both undergraduate programs of basic sciences and some technological careers. Despite its use, except in some very specific cases, it has been extensively employed as illustrative examples of the chemical concepts that were being demonstrated. Despite the numerous existing applications to comprehend the phenomena behind the development of new materials and biomedicine, it is difficult to find a conceptual introduction of molecular modeling applied to specific problems on the modern engineeries within the undergraduate programs. In the present work, it will be shown the introduction and adaptation of molecular modeling concepts within a new optional course for students coming from materials engineering, chemical engineering and biomedicine engineeries. Different approaches to problem-based and small project-based learning are presented to encourage the scientific spirit of students using techniques of molecular modeling that had not been visited throughout their studies and, thus, to discover their potential appliacation in a more specialized context

Fmoc–RGDS based fibrils: atomistic details of their hierarchical assembly

We describe the 3D supramolecular structure of Fmoc–RGDS fibrils, where Fmoc and RGDS refer to the hydrophobic N-(fluorenyl-9-methoxycarbonyl) group and the hydrophilic Arg-Gly-Asp-Ser peptide sequence, respectively. For this purpose, we performed atomistic all-atom molecular dynamics simulations of a wide variety of packing modes derived from both parallel and antiparallel ß-sheet configurations. The proposed model, which closely resembles the cross-ß core structure of amyloids, is stabilized by p–p stacking interactions between hydrophobic Fmoc groups. More specifically, in this organization, the Fmoc-groups of ß-strands belonging to the same ß-sheet form columns of p-stacked aromatic rings arranged in a parallel fashion. Eight of such columns pack laterally forming a compact and dense hydrophobic core, in which two central columns are surrounded by three adjacent columns on each side. In addition to such Fmoc¿Fmoc interactions, the hierarchical assembly of the constituent ß-strands involves a rich variety of intra- and inter-strand interactions. Accordingly, hydrogen bonding, salt bridges and p–p stacking interactions coexist in the highly ordered packing network proposed for the Fmoc–RGDS amphiphile. Quantum mechanical calculations, which have been performed to quantify the above referred interactions, confirm the decisive role played by the p–p stacking interactions between the rings of the Fmoc groups, even though both inter-strand and intra-strand hydrogen bonds and salt bridges also play a non-negligible role. Overall, these results provide a solid reference to complement the available experimental data, which are not precise enough to determine the fibril structure, and reconcile previous independent observations.Peer ReviewedPostprint (published version

Distribution of dopant ions around poly(3,4-ethylenedioxythiophene) chains: a theoretical study

The effect of counterions and multiple polymer chains on the properties and structure of poly(3,4-ethylenedioxythiophene) (PEDOT) doped with ClO4- has been examined using density functional theory (DFT) calculations with periodic boundary conditions (PBCs). Calculations on a one-dimensional periodic model with four explicit polymer repeat units and two ClO4- molecules indicate that the latter are separated as much as possible, with the salt structure and band gap obtained from such ClO4- distribution being in excellent agreement with those determined experimentally. On the other hand, DFT calculations on periodic models that include two chains indicate that neighboring PEDOT chains are shifted along the molecular axis by a half of the repeat unit length, with dopant ions intercalated between the polymer molecules acting as cement. In order to support these structural features, classical molecular dynamics (MD) simulations have been performed on a multiphasic system consisting of 69 explicit PEDOT chains anchored onto a steel surface, explicit ClO4- anions embedded in the polymer matrix, and an acetonitrile phase layer onto the polymer matrix. Analyses of the radial distribution functions indicate that the all-anti conformation, the relative disposition of adjacent PEDOT chains and the distribution of ClO4- dopant ions are fully consistent with periodic DFT predictions. The agreement between two such different methodologies allows reinforcing the microscopic understanding of the PEDOT film structure.Peer ReviewedPostprint (author's final draft

Detailed description of the molecular organization behind AFM images of polymer coatings: a molecular modeling approach

The current experimental techniques of surface characterization provide structural information on a much larger scale than that in which atomistic details can be observed. In this work, this size gap gets reduced by consistently combining different modeling techniques, which leads to describe the topographic profiles of thin polymer coatings at the atomistic level. A new modeling protocol that combines Monte Carlo generation with molecular dynamics relaxation has allowed us to reproduce the experimental topography of extremely thin poly(3,4-ethylenedioxythiophene) coating films using only the generated molecular models. The key element of this protocol relies on parceling the studied surfaces in independent small plots, of which detailed molecular models are built. Combining a finite number of independent models enables us to mimic the molecular organization of a large length of film that is orders of magnitude larger than the commonly used size in molecular models. The reconstructed area reproduces the thickness and roughness of very thin polymer coatings that were explicitly obtained for this study using very short electropolymerization times. This work shows a feasible way of visualizing with atomistic detail surfaces coated with polymeric films.Peer ReviewedPostprint (author's final draft

A molecular dynamics study on glucose molecular recognition by a non-enzymatic selective sensor based on a conducting polymer

Poly(hydroxymethyl-3,4-ethylendioxythiophene) (PHMeDOT), a very electroactive polythiophene derivative bearing a dioxane ring fused onto the thiophene ring and an exocyclic hydroxymethyl substituent, is able to electrocatalyze the oxidation of glucose in the presence of interferents (e.g. dopamine, uric acid and ascorbic acid) without the assistance of an enzymatic catalyst. In this work, after demonstrating that the chronoamperometric response of such polythiophene derivatives allows discrimination of glucose from fructose, the PHMeDOT¿sugar recognition mechanism has been investigated using atomistic computer simulations. More specifically, molecular dynamics simulations were conducted on model systems formed by a steel surface covered with a nanometric film of PHMeDOT, which was immersed in an aqueous environment with a few explicit sugar molecules (i.e. glucose or fructose). Analyses of the trajectories indicate that glucose interacts with PHMeDOT forming a well-defined network of specific hydrogen bonds. More specifically, glucose prefers to interact as a hydrogen bonding donor using the hydroxyl group tether to the main sugar ring, while PHMeDOT acts as the hydrogen bonding acceptor. Interestingly, (glucose)O–H¿O(PHMeDOT) interactions involve, as hydrogen bonding acceptors, not only the oxygen atoms of the dioxane ring but also the oxygen atom of the exocyclic hydroxymethyl substituent, which is a differential trend with respect to the other polythiophene derivatives that do not exhibit sensing ability. In contrast, fructose does not present such well-defined patterns of specific interactions, especially those that are distinctive because of the exocyclic hydroxymethyl substituent, making the experimental observations understandable.Postprint (author's final draft

Effect on the conformation of a terminally blocked, (E) ß,y-unsaturated o-amino acid residue induced by carbon methylation

Peptides are well-known to play a fundamental therapeutic role and to represent building blocks for numerous useful biomaterials. Stabilizing their active 3D-structure by appropriate modifications remains, however, a challenge. In this study, we have expanded the available literature information on the conformational propensities of a promising backbone change of a terminally blocked d-amino acid residue, a dipeptide mimic, by replacing its central amide moiety with an (E) Cß-C¿ alkene unit. Specifically, we have examined by DFT calculations, X-ray diffraction in the crystalline state, and FT-IR absorption/NMR spectroscopies in solution the extended vs folded preferences of analogues of this prototype system either unmodified or possessing single or multiple methyl group substituents on each of its four -CH2-CH-CH-CH2– main-chain carbon atoms. The theoretical and experimental results obtained clearly point to the conclusion that increasing the number of adequately positioned methylations will enhance the preference of the original sequence to fold, thus opening interesting perspectives in the design of conformationally constrained peptidomimetics.Postprint (author's final draft

3D structure of a Brucella melitensis porin: molecular modelling in lipid membranes

Brucella melitensis is a pathogenic bacterium responsible for brucellosis in mammals and humans. Its outer membrane proteins (Omp) control the diffusion of solutes through the membrane, and they consequently have a crucial role in the design of diagnostics and vaccines. Moreover, such proteins have recently revealed their potential for protein-based biomaterials. In the present contribution, the structure of the B. melitensis porin Omp2a is built using the RaptorX threading method. This is a 16-stranded ß-barrel with an a-helix on the third loop folding inside the barrel and forming the constriction zone of the channel, a typical feature of general porins such as PhoE and OmpF. The preferential diffusion of cations over anions experimentally observed in anterior studies is evidenced by the presence of distinct clusters of charges in the extracellular loops and in the inner pore. Docking studies support the previously reported hypothesis of Omp2a ability to aid maltotetraose diffusion. The monomer model is then assembled into a homotrimer, stabilized by the L2 loop involved in most of the interface interactions. The stability of the trimer is evaluated in three bilayers: pure 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), pure 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine (POPE) and a mixture of 1:1 of POPC/POPE. All-atom molecular dynamics simulations demonstrate the ß-barrel-structural stability over time even though a breathing-like motion is observed. Compared to the pure bilayers, the POPC/POPE better preserves the integrity of the protein and its channel. Overall, this work demonstrates the relevancy of the Omp2a model and will help to design new therapeutic agents and bioinspired nanomaterialsPeer ReviewedPostprint (author's final draft