Atomistic Simulations of Functionalized Nano-Materials for Biosensors Applications

Abstract

Nanoscale biosensors, a highly promising technique in clinical analysis, can provide sensitive yet label-free detection of biomolecules. The spatial and chemical specificity of the surface coverage, the proper immobilization of the bioreceptor as well as the underlying interfacial phenomena are crucial elements for optimizing the performance of a biosensor. Due to experimental limitations at the microscopic level, integrated cross-disciplinary approaches that combine in silico design with experimental measurements have the potential to present a powerful new paradigm that tackles the issue of developing novel biosensors. In some cases, computational studies can be seen as alternative approaches to assess the microscopic working mechanisms of biosensors. Nonetheless, the complex architecture of a biosensor, associated with the collective contribution from “substrate–receptor–analyte” conjugate in a solvent, often requires extensive atomistic simulations and systems of prohibitive size which need to be addressed. In silico studies of functionalized surfaces also require ad hoc force field parameterization, as existing force fields for biomolecules are usually unable to correctly describe the biomolecule/surface interface. Thus, the computational studies in this field are limited to date. In this review, we aim to introduce fundamental principles that govern the absorption of biomolecules onto functionalized nanomaterials and to report state-of-the-art computational strategies to rationally design nanoscale biosensors. A detailed account of available in silico strategies used to drive and/or optimize the synthesis of functionalized nanomaterials for biosensing will be presented. The insights will not only stimulate the field to rationally design functionalized nanomaterials with improved biosensing performance but also foster research on the required functionalization to improve biomolecule–surface complex formation as a whole.

Tuning gold-based surface functionalization for streptavidin detection: A combined simulative and experimental study

“…Our results show that the functionalized biotins are capable of specifically capturing SA from the surface–liquid interface with micro-molar affinity. Here, the SA–biotin pair has been used as a proof-of-concept in view of a further challenge, namely the design of more complex devices in the form of coupled binders ( Dutta et al, 2022 ) or antibody fragments ( Yang and Shah, 2020 ) in the quest for biosensors with enhanced binding affinity.…”

Current Trends and Changes in Use of Membrane Molecular Dynamics Simulations within Academia and the Pharmaceutical Industry

“…Of note are special features that can be incorporated into MD such as x-ray or photon bombardment, surface structures such as silicon or graphite, applied electronic current, radioactive elements, and others important in medicine or general biology. These are mentioned in most of the general software manuals with NAMD, LAMMPS and Gromacs providing great detail, but are usually utilized by engineers for such activities as Plasmon chip design, diagnostic components, or equipment in the medical fields [ 7 , 54 , 55 ]. Nevertheless, these constitute one area of focus related to biologics, especially in basic testing phases such as kinetics or expected interactions related to membranes.…”

“…Additional examples include peptide antibiotics, cyclic modified peptides for cancer therapies, afamatrix chips, diagnostic chips and in some cases modified Au-lipid nanoparticles as delivery systems. All of these have utilized MD in the design process and included studies in safety as well as proof of the principle aspects associated with the patent process or applications themselves [ 55 , 168 ].…”

DockSurf: A Molecular Modeling Software for the Prediction of Protein/Surface Adhesion

“…Describing and understanding the nature of molecular recognition between an inorganic surface and a protein is paving the way toward rationalization, optimization, and prediction of many biotechnology devices . This enables the design and development of biomaterials, drug delivery systems, and biosensors with enhanced performance and biocompatibility. Second, studying protein–surface interactions provides insights into the fundamental mechanisms governing biological processes at interfaces, shedding light on cellular adhesion, signaling, and biomolecular recognition .…”