Macromolecular Conformational Analyses And Its Applications In SEC,DNA Confined In Nanochannel And Protein-polymer Conjugations

Macromolecules, also known as polymers, can be divided into synthetic polymers and natural polymers. Because of its high molecular weight, polymers have more complicated conformational properties than small molecules. For linear or ring polymers, the most commonly used conformational properties are characterizations of sizes of the chains, such as the mean square radius of gyration, end-to-end distance, and other characterizations about the flexibility or the shape of the polymers. For natural polymers, especially for proteins, conformations due to the folding and rotational motion of peptide chains, have a great influence on the protein activity. Therefore it’s necessary to analyze the conformational properties for macromolecular systems. This research forcused on the conformational analyses of macromolecules, and used macromolecular theory and computer simulations to study systems.The three macromolecular system are:（1） The analysis of conformational properties of bridged polycyclic ring polymers, and its applications in Size Exclusion Chromtography.（2） The force-extension relationship of DNA confined in nanochannels.（3） The conformational analyses of two kinds of polymer-protein conjugations. Details are follows.（1） We calculated the mean square radius of gyration, mean span dimension, and geometric shrinking factors of an ordinary unknotted ring（f=2）, a knot-trefoil ring（f=2）, a θ-shaped（f=3）, and a δ-graph（f=4） flexible bridged polycyclic rings by three approaches. The first approach is rigorous calculations based the phantom Gaussian chain model, which neglects the excluded volume interactions among chain segments and the topological constraints due to the non-crossability of chain sections. The second approach is by computer simulations based on the popular Kremer-Grest bead-spring model, and the last approach relies on a rather simple Flory-type arguments. The last approach is particularly suitable for a qualitative understanding of the shrinking in size of bridged polycyclic ring polymers relative to that of a linear chain of the same molar mass with the increase of f.Using the CABS method to study the equilibrium partition coefficient（ K） of the mentioned polymers in a cylindrical pore with inert surfaces, and examined the performance of the mean span dimension theory in predicting the ratio G=M_SEC/M_true The M_SEC is the apparent peak molecular weight measured in SEC by conventional column calibration and M_True is the “true” molecular weight. It is found that the mean span dimension theory, although supported by the neat universality in the calculated SEC-mode equilibrium partition coefficients, predicts the G parameters somewhat smaller than the available experimental data in the literature.（2） We used Metropolis Monte Carlo simulation method to investigate the elongation of a semi-flexible chain model（ds DNA） with excluded volume interactions, which confined in different sizes of nanochannels and under different tensile force. The results with a simple worm-like touching bead model are analyzed with an empirical formula proposed by Chen et al.（3） We used Molecular Docking to study the interactions between tissue type Plasminogen Activator（ t PA） and two kinds of ligands（ARMAPE and ARMAPE-OEGMA）, it’s found that the interactions between t PA and the peptide modified with polymer（POEGMA） are stronger. And we used Molecular dynamics to study the conformations of mutant Inorganic pyrophosphatase（PPase）, which is conjugated with two different chain transfer agents CTA-pyridine（CTA-a） and CTA-maleimide（CTA-b）, respectively. It’s found that conjugating with CTA-b results in bigger transformation for the structure of PPase.