Study of conductive polymers, biomolecules and their hybrids through computational approaches
- Autores: Jordi Triguero Enguídanos
- Directores de la Tesis: Carlos Alemán Llansó (dir. tes.), David Zanuy Gomara (codir. tes.)
- Lectura: En la Universitat Politècnica de Catalunya (UPC) ( España ) en 2019
- Idioma: español
- Tribunal Calificador de la Tesis: Xavier Barril Alonso (presid.), Juan Torras Costa (secret.), Gianfranco Bocchinfuso (voc.)
- Programa de doctorado: Programa de Doctorado en Polímeros y Biopolímeros por la Universidad Politécnica de Catalunya
- Materias:
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- Resumen
In this Thesis, different theoretical approaches designed to study a wide interval of length- and/or time-scales have been used to examine the microscopic properties of chemical systems with varying degrees of complexity and size. Firstly, the conformational preferences and optical properties of a tripeptide derived from the RGD sequence, the unit of a cell adhesive activity domain in adherent proteins, have been analyzed. Calculations on this peptide, which contains an exotic amino acid bearing a 3,4-ethylenedioxythiophene (EDOT) ring as side group, have been performed using DFT and time depending DFT methods. Results indicate that the bioactive characteristics of the RGD sequence become unstable in presence of the new residue because of both the steric hindrance caused by the EDOT side group and the repulsive interactions between the oxygen atoms belonging to the backbone amide groups and the EDOT side group. This information has been used to propose some chemical changes oriented to improve the bioadhesive properties. The interaction of a cell penetrating tetrapeptide, RPAR, adsorbed onto a gold substrate and the deposition of a pre-assembled peptide-polymer conjugate, cyc[(L-Gln-D-Ala-L-Lys-D-Ala)2] coupled with two poly(n-butyl acrylate) blocks, onto a mica substrate have been examined through molecular dynamics (MD). Results indicate that RPAR binds both the (100) and (111) gold surface facets. The conformation of the adsorbed peptide differs considerably from the bioactive conformation. However, the new conformations are not stabilized by strong intramolecular interactions. Accordingly, gold nanoparticles can be considered as suitable vehicles for the transport and targeted delivery of this CendR peptide. For the pre-assembled peptide-polymer conjugate, a theoretical approach that simulates the selective and progressive desolvation of the nanotube-like assembly has been used, demonstrating that the solvent presence during deposition is the main responsible for the unexplained conformational preferences of the acrylate blocks. When the proportion of solvent drops, the loss of many attractive solute-solvent interactions induces a meaningful increase in the number of torsions. MD has been also used to understand the impact of the solvation medium and the action of a detergent in the structure of a representative outer membrane protein (OMP). Calculations show the destabilization of the protein in water, while in presence of detergent molecules in solution or the bilayer induce a partial and complete protective effect, respectively. Combining stochastic algorithms and MD simulations the atomistic details of polymer coatings deposited over metal surfaces have been modeled to reproduce the experimentally observed topographic features of poly(3,4-ethylenedioxythiophene), PEDOT, deposited onto stainless steel. Results have provided an excellent model system to test the developed modeling strategy. Multi-phasic simulations have been conducted to explain the influence of protein···polymer interactions in the antimicrobial biocapacitors activity of lysozyme (LYZ)-containing PEDOT electrodes through atomistic MD calculations. Two models have been investigated: i) a biphasic system in which the protein was adsorbed onto the surface of PEDOT, PEDOT/LYZ; and ii) a biocomposite in which the LYZ was homogeneously distributed inside the PEDOT matrix, P(EDOT-LYZ). MD simulations have been performed in absence and presence of electric fields, the latter mimicking the one originated by the voltage cell difference in biocapacitors. In PEDOT/LYZ electrodes, the loss of biological activity has been attributed to the anisotropy of the PEDOT···LYZ electrostatic interactions. In contrast, anisotropic effects are minimized in P(EDOT-LYZ), conserving activity. The bactericidal activity of PEDOT/LYZ and P(EDOT-LYZ) biocapacitors is independent of the electric field applied or supplied during charge-discharge processes.
