Caracterização molecular de biopolímeros em solução utilizando simulação computacional

Abstract

Computer simulation methods were used to characterize the structure and molecular properties of natural and synthetic biopolymers in aqueous solution. The polysaccharides chitin and chitosan, and aliphatic polypeptides were studied. The interest on the chitin and chitosan biopolymers is because of their biodegradability, biocompatibility and potential use as pharmaceutical and technological product. Molecular dynamics simulations have been used to characterize the structure and the solubility of the chitins and chitosans in aqueous solution. The simulated systems were composed by solvated chains, and nanoparticles composed by chains packed in a parallel and anti-parallel fashion, with different percentage and distribution of acetyl groups. The 100% acetylated chitin, whether isolated or in the form of α/β-chitin, adopt the 2-fold helix conformation with φ and ψ values similar to those on crystalline state. The ionic strength affects the kinetics, but not the conformational equilibrium. In solution, the intramolecular hydrogen bond HO3(n)···O5(n+1) responsible for the 2-fold helical motif is stabilized by hydrogen bonding to water molecules in a well-defined orientation. On the other hand, chitosan with small percentage and random distribution of acetil groups can adopt five distinct helical motifs and its conformational equilibrium is highly dependent on pH. The hydrogen bond pattern and solvation around the O3 atom of insoluble chitosan (basic pH) are nearly identical to those quantities in chitin. Chitin and chitosan nanoparticles with block distribution of acetyl groups favor the formation of intermolecular hydrogen bonds and hydrophobic interactions, resulting in more stable aggregates. The water mobility and orientation around polysaccharide chain (highly affected by electrostatic forces) is responsible for the aggregation and solubility of the chitin and chitosan biopolymers. Moreover, a sequential QM/MM methodology is used to study the α-helix stability of aliphatic polypeptides in water solution. The understanding of the folding process is one of the greatest challenges of biophysics, and the first step is the understanding of the formation and stabilization of the secondary structure of a polypeptide. The calculated heat of formation and free energy of solvation showed that the size of side chain is directly related to the α-helix stability. The results suggest that the helix-coil transition of a polypeptide is governed by the equilibrium between the energy used in the folding process and the energy released in the solvation process, showing the solvent effect on α-helix stabilization. The validation of the sequential QM/MM methodology showed that this method is suitable to study the helix-coil transition of polypeptides in solution. The methodology is therefore useful to study solvation effects on the properties of compounds with many conformational degrees of freedom.