Theoretical Investigation of Self-Assembled Peptide Nanostructures for Biotechnological and Biomedical Applications



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In this dissertation, molecular simulation techniques are used for the theoretical prediction of nanoscale properties for peptide-based materials. This work is focused on two particular systems: peptide nanotubes formed by cyclic-D,L peptide units and peptide nanotubes formed by phenylalanine dipeptides [-Phe-Phe-]. Mechanical characterization of cyclic peptide nanotubes is a challenging problem due the anisotropy resulting from the nature of their molecular interactions. To address rigorously the thermo-mechanical stability of cyclic peptide nanotubes (CPNTs), a homogeneous deformation method combined with the generalized elasticity theory and molecular dynamics simulations (MD) were used for the calculation of second order anisotropic elastic constants. The results for anisotropic elastic constants, yield behavior and engineering Young?s modulus show remarkable mechanical stability for these materials supporting experiments for the development of their applications. Furthermore, the heat capacity, thermal expansion coefficient and isothermal compressibility were predicted using numerical difference methods and molecular dynamics. In order to understand the transport properties of confined water in cyclic peptide nanotubes, the influence of nanotube diameter was studied and self-diffusion coefficient, dipole correlation functions and hydrogen bond probabilities were calculated via molecular dynamics and statistical mechanics. Enhanced transport and higher diffusion rates for water were obtained in cyclic peptide nanotubes (CPNTs) compared with commonly used biomedical channels like carbon nanotubes (CNTs). The greater transport efficiency in CPNTs is attributed to the hydrophilic character and high hydrogen bonding presence along their tubular structure, versus the hydrophobic core of CNTs. One of the most important opportunities for cyclic peptide nanotubes is their utilization as artificial ion channels in antibacterial applications. Here, molecular dynamics methods were used to investigate the effect of confinement on the transport properties of Na+ and K+ ions under the influence of electric field; the ion mobility, selectivity, radial distribution function, coordination number and effect of temperature were studied and results from simulations proved their ability to transport ions. Additionally, the molecular organization of phenylalanine dipeptides into ordered peptide nanotubes was investigated, a model for the molecular structure of these nanotubes was proposed and optimized through molecular simulations; a helical pattern was found and characterized. Thermal stability results show that phenylalanine dipeptide nanotubes are stable up to about 400K; above this temperature, a significant decrease in hydrogen bonding was observed and the perfect pattern was altered. Findings from this work open new opportunities for research in the area of peptide based materials and provide tools and methods to study these systems efficiently at nanoscale.