The work investigates molecular origin of change in conformational states with changes in local environment and with the structure of modifications done on to the polar polymer. The work is split into two major parts based on origin of the polar polymer. In the first part, a synthetic polyelectrolyte, poly(vinyl amine) (PVAm), and their hydrophobic derivatives are investigated for their pH-responsive nature in dilute aqueous solution. While in the second part, a natural polyelectrolyte/polar polymer, Oxytocin is investigated for its dominant conformations in dilute aqueous solution, effect of temperature and effect of PEGylation structure of them is investigated.
Although polyelectrolytes is a multi-billion dollar industry, the PVAm became commercially available only after the year 2000. While the patents and publications by companies like Air Products, BASF and Mitsubishi appeared in mid-1990s systematic molecular simulations study of PVAm and its derivatives is absent. In the current work, MD simulations of PVAm and its hydrophobic derivatives (homopolymers and copolymers) were studies to understand molecular nature of their pH responsive behaviour. The simulations were carried out with explicit water to probe the role of Charge-charge repulsion and hydrophobic interaction, hydration and counterion condensation in their pH responsive nature. The hydrophobic interactions were varied through variation in substitution structure and degree of substitution.
Therapeutic peptides rapidly growing multi-billion dollar industry. Oxytocin is a therapeutic peptide listed as essential medicine by World Health Organization (WHO). The peptide is thermally unstable and requires to be stored at 2-8 ℃. OT, The nonapeptidic hormone, has a Tocin ring composed of six amino acid formed through disulphide linkage followed by a tripeptide tail. Replica exchange MD simulations were used to determine equilibrium conformations of OT in aqueous solution which then were subjected to MD simulation study upon PEGylation to study the effect of PEG on the dominant conformations. For the first time we show two dominant conformations comprising of ~ 80 % of total population differ at Residue 3 and 4 of the Tocin ring. The results were compared with NMR observables and older simulation literature and the results are discussed. Effect of PEGylation on to OT structure is also reported.