Impact of Silane Monolayers on the Adsorption of Streptavidin on Silica and Its Subsequent Interactions with Biotin: Molecular Dynamics and Steered Molecular Dynamics Simulations

Abstract

Protein adsorption on surfaces is used in analytical tools as an immobilization mean to trap the analyte to be detected. However, protein adsorption can lead to a conformational change in the protein structure, resulting in a loss of bioactivity. Here, we study the adsorption of the Streptavidin -Biotin complex on amorphous SiO 2 surfaces functionalized with five different silane selfassembled monolayers by all-atom Molecular Dynamics simulations. We find that the Streptavidin global conformational change increases linearly with the adsorption energy, which depends, as well as the nature of residues with high mobility, on the alkyl chain length and head group charge of silane molecules. Effects on interactions with Biotin are further investigated by Steered Molecular Dynamics (SMD) simulations, which mimics Atomic Force Microscope (AFM) spectroscopy with the Biotin attached on the tip. We show the combined effects of adsorptioninduced global conformational changes and of the position of residues with high mobility on the force of Biotin detachment. By comparing our results to experimental and SMD detachment forces obtained in water, without any surface, we conclude that silane with uncharged and short alkyl chains allow Streptavidin immobilization, with high adsorption energy, while keeping Biotin interactions better than silanes with long alkyl chains or charged head-groups.

Molecular dynamics study on membrane fouling by oppositely charged proteins

“…Firstly, despite the same conditions, the different initial orientations lead to significantly different trajectories of the protein, with predominantly low d values in some cases whereas predominantly high d values were obtained in other cases. The dominant influence of initial orientation agrees with earlier simulation studies of different proteins 30,49,53 . Secondly, although electrostatic considerations would imply greater lysozyme–membrane affinity than that of α‐lactalbumin, the d values for lysozyme do not appear to be distinctly smaller.…”

“…Because of the variation of the nature of the residues throughout the protein, the interaction energies depend on which residues are oriented so that they are able to interact with the membrane 31,52,53 . Depending on the orientation of the protein, metastable states are known to be attained instead of the minimum energy state 54 .…”

“…Depending on the orientation of the protein, metastable states are known to be attained instead of the minimum energy state 54 . To account for such variations, the simulations for each protein were initialized using one of six orientations, which are 90° rotations about the x ‐axis or y ‐axis, as per earlier studies 33,53 . Such multiple different orientations allow for different domains of the macromolecular protein to interact with the membrane initially.…”

Membrane fouling by lysozyme: Effect of local interaction

“…Considering the large size and structural heterogeneity of lysozyme, different initial orientations of the lysozyme were considered, since it is well‐acknowledged that initial orientation affects adsorption behavior 55,56 . Regarding capturing representative orientations, an earlier study suggested 90° orientations 57 . In this study, six initial orientations were used, because too few may not be sufficiently representative particularly in view of metastable states, 35 while too many would incur high computational costs.…”

“…In this study, six initial orientations were used, because too few may not be sufficiently representative particularly in view of metastable states, 35 while too many would incur high computational costs. As illustrated in Figure 1, other than the orientation shown (i.e., as downloaded from the PDB and designated a x = 0°, a y = 0°), three additional rotations about the x ‐axis (i.e., a x = 90°, a y = 0°; a x = 180°, a y = 0°; and a x = 270°, a y = 0°) and two additional rotations about the y ‐axis (i.e., a x = 0°, a y = 90°; and a x = 0°, a y = 270°) were investigated 57 . For the quantification of parameters such as interaction energy or rotational angle, the average value was taken from these six runs.…”