(6lh) Design of Protein-Polyelectrolyte Complexes

PI: Prof. Venkat Ganesan, University of Texas, Austin

Keywords: Proteins, Single Chain in Mean Field, Polyelectrolytes, Monte Carlo, Polymer, Electrostatics. Coacervation.

A widely used technique to stabilize proteins is to entrap those using highly charged polyelectrolytes. This methodology is used in stabilizing proteins in biosensors to increase their shelf life, extraction of proteins in food industries like in preparing whey powder and forming new biomaterials that can mimic properties of commercial non-biodegradable polymeric materials. The objective of our research is to build a generalized computational framework that can bring a comprehensive understanding of the physicochemical aspects underlying the structure and rationally guide the efforts to design and optimize protein and polyelectrolyte systems to obtain desired properties. To model this system, we have developed a coarse-grained multibody simulation framework which involves a combination of single chain in mean field (SCMF) simulation and hybrid particle field framework. To accommodate the weak proteins and polyelectrolytes, we used a hybrid of constant pH method and the existing SCMF framework in a semi-grand canonical system.

The structure and phase behaviors that manifest in the protein polyelectrolyte systems are understood as a consequence of the resulting electrostatic interaction and the polymer mediated interaction. In a mixture of low homogeneously charged proteins and polyelectrolytes, clusters are formed from direct aggregation of proteins, due to attractive interaction led by depletion of polymers. However, at higher charge, oppositely charged polyelectrolytes form a bridge between the otherwise electrostatically repelling charged proteins. Charged macromolecules are found to experience increased repulsion when the dielectric constant of the proteins is lower than that of the solvent. However, the influence of the dielectric contrast is found to diminish with an increase in the protein volume fraction and its charge. Our results demonstrated, when charge heterogeneity in protein is included, irrespective of the net charge of the proteins, charge heterogeneity can exert a significant influence on the resulting characteristic of the aggregates, in some cases leading to a transformation from polymer-bridged complexes into direct particle phase. A very crucial aspect of the system is when the side chain of the amides or the polyelectrolytes are weak acid or bases. In our research so far, we have discovered that both weak and strong polyelectrolytes have a higher tendency to form bridges for a weak protein than a strong protein of the same charge. In the broadest terms, our work will bring a comprehensive understanding of the physicochemical aspects underlying the structure and phase behavior of protein and polyelectrolyte mixtures and help in rationally engineering the proteins.

Research Experience: I am also involved in a project which aims at understanding the transport properties of water and salt ions, in the mesoscopic pore structures in the membranes formed by the self-assembly of multi-block copolymers. This project is led by a postdoctoral researcher in our group. This study is crucial for designing advanced water purification membranes for experimental collaborators. This study relies on using dissipative particle dynamics (DPD) simulations using LAMMPS. During my master’s program, I investigated the stability criterion of two immiscible charged liquid layers present in biological systems like lipid bilayers. The research relied on using analytical techniques involving linear perturbation analysis.

Areas of Interest for Postdoc: As a postdoc, I want to explore the areas of computational therapeutics, molecular Biophysics and/or projects related to computer aided drug discovery, drug design. In addition to diversifying my technical skill sets, I want to focus more on collaborating closely with experimental works.