In silico study of substrate chemistry effect on the tethering of engineered antibodies for SARS-CoV-2 detection: Amorphous silica vs gold

Abstract

The influence of the properties of different solid substrates on the tethering of two antibodies, IgG1-CR3022 and IgG1-S309, which were specifically engineered for the detection of SARS-CoV-2, has been examined at the molecular level using conventional and accelerated Molecular Dynamics (cMD and aMD, respectively). Two surfaces with very different properties and widely used in immunosensors for diagnosis, amorphous silica and the most stable facet of the face-centered cubic gold structure, have been considered. The effects of such surfaces on the structure and orientation of the immobilized antibodies have been determined by quantifying the tilt and hinge angles that describe the orientation and shape of the antibody, respectively, and the dihedrals that measure the relative position of the antibody arms with respect to the surface. Results show that the interactions with amorphous silica, which are mainly electrostatic due to the charged nature of the surface, help to preserve the orientation and structure of the antibodies, especially of the IgG1-CR3022, indicating that the primary sequence of those antibodies also plays some role. Instead, short-range van der Waals interactions with the inert gold surface cause a higher degree tilting and fraying of the antibodies with respect to amorphous silica. The interactions between the antibodies and the surface also affect the correlation among the different angles and dihedrals, which increases with their strength. Overall, results explain why amorphous silica substrates are frequently used to immobilize antibodies in immunosensors.

Enzyme immobilization studied through molecular dynamic simulations

“…AuNPs were also prevalently functionalized with organic thiol molecules prior immobilization leading to a self assembled monolayer, which will be discussed in the next section. Although out of the scope of the current review, in the last years, these computational studies have not been limited only to the study of enzymes, but they also have been applied to assess the binding of antibodies, nanobodies and others with nanoparticle surfaces ( Xiao et al, 2018 ; Simões et al, 2021 ; Martí et al, 2022 ).…”