Molecular Modeling and Simulation Tools in the Development of Peptide-Based Biosensors for Mycotoxin Detection: Example of Ochratoxin

Abstract

Mycotoxin contamination of food and feed is now ubiquitous. Exposures to mycotoxin via contact or ingestion can potentially induce adverse health outcomes. Affordable mycotoxin-monitoring systems are highly desired but are limited by (a) the reliance on technically challenging and costly molecular recognition by immuno-capture technologies; and (b) the lack of predictive tools for directing the optimization of alternative molecular recognition modalities. Our group has been exploring the development of ochratoxin detection and monitoring systems using the peptide NFO4 as the molecular recognition receptor in fluorescence, electrochemical and multimodal biosensors. Using ochratoxin as the model mycotoxin, we share our perspective on addressing the technical challenges involved in biosensor fabrication, namely: (a) peptide receptor design; and (b) performance evaluation. Subsequently, the scope and utility of molecular modeling and simulation (MMS) approaches to address the above challenges are described. Informed and enabled by phage display, the subsequent application of MMS approaches can rationally guide subsequent biomolecular engineering of peptide receptors, including bioconjugation and bioimmobilization approaches to be used in the fabrication of peptide biosensors. MMS approaches thus have the potential to reduce biosensor development cost, extend product life cycle, and facilitate multi-analyte detection of mycotoxins, each of which positively contributes to the overall affordability of mycotoxin biosensor monitoring systems.

Computational Studies of a DNA-Based Aptasensor: toward Theory-Driven Transduction Improvement

“…The available literature on molecular modeling studies of sensing architectures including an immobilized bioreceptor is scarce. Some recent articles deal with peptide-based systems (i.e., ochratoxin, carboxyhemoglobin, and dopamine), but very few engage a nucleic acid sequence as a receptor. Puangmali and collaborators have published a sequence of articles in which they deciphered the mechanisms of naked-eye colorimetric aptasensors, first for the detection of ochratoxin A, then on cysteamine-capped and citrate-capped gold nanoparticles for 8-oxo-dG detection, using molecular dynamics (MD) simulations, with the latter two also showing experimental validation.…”

Screening and application of peptamers

“…异硫氰 酸荧光素标记的肽适体可通过共价结合的方法固定在 多孔硅微腔, 此方法对细菌分选酶A的检测限可达到 8×10 −14 mol/L [82] . 基于肽适体的传感器设计可以实现 霉菌毒素的检测, OTA是其典型示例 [94] .…”

Computational studies of a DNA-based aptasensor: toward theory-driven transduction improvement.

“…The available literature on molecular modeling studies of sensing architectures including an immobilized bioreceptor is scarce. Some recent articles deal with peptide-based systems (i.e., ochratoxin 17 , carboxyhemoglobin 18 , dopamine 19 ) but very few engage a nucleic acid sequence as a receptor. Choodet et al deciphered the mechanisms of naked-eye aptasensors, based on citrate-capped gold nanoparticles (AuNPs), for 8-oxo-dG detection, using molecular dynamics (MD) simulations 19 .…”