(595e) A Charged Surface Induces Oriented Alignment of Like-Charged Peptides and Reduces Their Aggregation
AIChE Annual Meeting
2013
2013 AIChE Annual Meeting
Engineering Sciences and Fundamentals
Biomolecules at Interfaces I
Thursday, November 7, 2013 - 9:35am to 9:50am
Aggregation of protein folding intermediates is a critical issue encountered in protein refolding for the production of recombinant proteins, so inhibiting protein aggregation is essential for enhancing in vitro protein refolding yield. Recently, it was found that like-charged ion-exchange particles were highly efficient for suppressing the aggregation, leading to a significant increase in protein refolding yields (G.-Z. Wang, X.-Y. Dong, Y. Sun, Biotechnol. Bioeng. 2011, 108, 1068). The working mechanism of like-charged resin was proposed to be the formation of spatially oriented alignment of protein molecules induced by the repulsion of protein dipoles by the like-charged surfaces. This maximizes the electrostatic repulsion between protein molecules and leads to the inhibition of protein aggregation. This work was designed to examine this hypothesis. All-atom (AA) models of positively charged and neutral surfaces were constructed, while a dipeptide, KL, with a net charge of +1e (2 positive charges and 1 negative charge) at pH 7, was utilized to mimic a protein molecule that has an uneven surface charge distribution with an electric dipole. Two peptide molecules were equilibrated in an aqueous solution, and then placed over a surface to investigate their molecular behaviors (steric alignment and distribution) and molecular interactions by molecular dynamics simulation. It is found that both the peptide molecules are excluded from the like-charged surface within a few nanoseconds. During this process, oriented alignment forms immediately after the beginning of the simulation. Namely, the electric dipoles become perpendicular to the charged surface with the negatively charged end facing the surface. Moreover, inter-molecular interaction energy reveals the increase of electrostatic repulsion between the two orientedly aligned peptide molecules. By contrast, neither oriented alignment nor increase of electrostatic repulsion between two dipeptides is observed near the neutral surface. This work has thus demonstrated that charged surface can induce oriented alignment of like-charged peptide molecules, leading to the increase of electrostatic repulsion between peptide molecules, which would inhibit protein aggregation in a protein folding process as observed in experiments.