Surface charge distribution: a key parameter for understanding protein behavior in chromatographic processes

Abstract

Multi-component adsorption of proteins still requires a better understanding of local phenomena to im-prove the development of predictive models. In this work, all-atom Molecular Dynamics (MD) simula-tions were used to investigate the influence of protein charge distribution on the adsorption capacity. The simultaneous adsorption of α-chymotrypsin and lysozyme on a cation exchanger, SP Sepharose FF, was studied through MD simulations and compared to macroscopic isotherm experiments. It appears that the charge distribution is a relevant information to better understand specific phenomena, such as a multilayer adsorption caused by the particular electrostatic profile of α-chymotrypsin. Therefore, MD simulations seem to be an interesting way to visualize and highlight these behaviors. Ion-exchange chromatography Proteins Molecular Dynamics Simultaneous adsorption Charge distribution

Investigation of membrane fouling using molecular dynamics simulation

“…Similar observations have been made by other studies, wherein a positively arginine residue was found to play important roles in the anchoring of the overall negative protein to the negative surface [125,159,166]. Expectedly, hydrophobic residues are preferentially adhere to hydrophobic surfaces [117,119], while hydrophilic ones exhibit affinity to hydrophilic surfaces [122], implying that the local regions of proteins need to be scrutinized to determine anchoring onto the membrane or not [114].…”

“…As shown by the simulation snapshots and evolution of separation distance (i.e., foulant-surface and foulant-foulant) in Fig. 2-5D, Tournois et al [114] proved that α-chymotrypsin is able to adsorb on top of the adsorbed lysozyme to form a multilayer structure, with the interaction between α-chymotrypsin and the ligand surface hindered by the electrostatic field of lysozyme. Similarly, Tiwari et al [118]…”

“…The evolution of separation distance with respect to time is usually used to identify whether adsorption has occurred, and thereby allows for comparing the fouling potential of different foulants or membranes. Since both foulant and membrane are made of many atoms, the distance between these two entities can be defined either by (i) the minimum distance in between [28,31,34,114]; (ii) distance between selected atoms [95]; (iii) distance between the centers of mass (COM) [93,98]. As shown in Fig.…”

“…For instance, the MD system can be designed in such a way that some foulant are preadsorbed to the membrane surface. There have been a few studies on foulant-foulant interaction by including more than one foulant molecule in the system [93,114,118],…”