Orientation of Adsorbed Antibodies on Charged Surfaces by Computer Simulation Based on a United-Residue Model

Abstract

In this work, we develop a new residue-based protein-surface interaction potential model. With this model, the adsorption and orientation of two antibodies, IgG1 and IgG2a, are studied by Monte Carlo simulations. Effects of surface charge density and sign, and solution ionic strength are examined in our simulations. Simulation results show that van der Waals and electrostatic interactions codetermine the orientation of adsorbed antibodies. At low surface charge density and high solution ionic strength, where van der Waals interactions dominate, both IgG1 and IgG2a exhibit multiple orientations. At high surface charge density and low solution ionic strength, where electrostatic interactions dominate, there are preferred orientations for these two antibodies on both positively and negatively charged surfaces, which are verified by experimental results. Due to a smaller dipole moment, IgG2a has more possible orientations than IgG1. IgG1 adsorbed on a positively charged surface shows an "end-on" orientation, which is well suited for biosensor applications. The simulation methodology and model could be directly applied to predict the adsorption and orientation of other proteins and to provide a fundamental understanding of their behavior on surfaces at the molecular level.

Understanding protein adsorption phenomena at solid surfaces

“…In quite a number of recent studies empirical all-atoms force field methods were successfully applied to determine the preferred orientations of surface bound proteins [275][276][277][278][280][281][282][283][284][285][286], to visualize conformational rearrangements upon adsorption [276][277][278]287], and to explore effects on the solvation shell [277,288,289]. By using a combination of MC and MD simulations to study the adsorption of the proteins IgG and cytochrome c (Cyt-c), Zhou et al were able to show that there is a surface charge-driven mechanism of protein orientation [281][282][283]. In particular they simulated Cyt-c adsorption on a self assembled monolayer terminating with carboxylic functionalities at varying dissociation degrees, i.e.…”

Modulating cell adhesion and spreading by control of FnIII7–10 orientation on charged self‐assembled monolayers (SAMs) of alkanethiolates

“…Details about the residue-based model can be found elsewhere. 5 Monte Carlo (MC) simulations were carried out with this residue-based protein-surface interaction potential in an implicit solvent with an ionic strength of 0.15M. An ionic dissociation rate of 10% was assumed for both SAMs.…”

Structural variation of alpha-synuclein with temperature by a coarse-grained approach with knowledge-based interactions

“…are common procedures in coarse-grained modeling. [38][39][40][41][42][43][44][45][46][47][48][49] Knowledgebased contact matrix [50][51][52][53][54][55][56][57] (derived from an ensemble of frozen structures of protein available at the protein data bank (PDB)) has been extensively used to develop phenomenological residue-residue interactions to understand the folding dynamics of proteins. As in our previous investigations, 56,57 we will use the classical knowledge-based interaction due to Miyazawa and Jernigan (MJ) 51 and one of its improved versions by Betancourt and Thirumalai (BT) 53 to study the structure and dynamics of un-solvated ASN as a function of temperature.…”