Abstract
Biosensing platforms based on peptide recognition provide a cost-effective and stable alternative to antibody-based capture and discrimination of ochratoxin-A (OTA) vs. ochratoxin-B (OTB) in monitoring bioassays. Attempts to engineer peptides with improved recognition efficacy require thorough structural and thermodynamic characterization of the binding-competent conformations. Classical molecular dynamics (MD) approaches alone do not provide a thorough assessment of a peptide’s recognition efficacy. In this study, in-solution binding properties of four different peptides, a hexamer (SNLHPK), an octamer (CSIVEDGK), NFO4 (VYMNRKYYKCCK), and a 13-mer (GPAGIDGPAGIRC), which were previously generated for OTA-specific recognition, were evaluated using an advanced MD simulation approach involving accelerated configurational search and predictive modeling. Peptide configurations relevant to ochratoxin binding were initially generated using biased exchange metadynamics and the dynamic properties associated with the in-solution peptide–ochratoxin binding were derived from Markov State Models. Among the various peptides, NFO4 shows superior in-solution OTA sensing and also shows superior selectivity for OTA vs. OTB due to the lower penalty associated with solvating its bound complex. Advanced MD approaches provide structural and energetic insights critical to the hapten-specific recognition to aid the engineering of peptides with better sensing efficacies.
Highlights
IntroductionAspergillus ochraceus and Penicillium verrucosum [1,2]
Ochratoxins are a group of chemically related mycotoxins produced by storage fungi likeAspergillus ochraceus and Penicillium verrucosum [1,2]
Advanced sampling and predictive modeling were used for the in-solution characterization of the affinity and selectivity of four unique peptides (a) hexamer (SNLHPK); (b) octamer (CSIVEDGK); (c) NFO4 (VYMNRKYYKCCK); and (d) 13-mer (GPAGIDGPAGIRC) known for their molecular recognition of ochratoxins
Summary
Aspergillus ochraceus and Penicillium verrucosum [1,2]. These low-molecular-weight chemicals are polyketides with a dihydro-isocoumarin moiety linked to β-phenylalanine [1]. Though at least three different structural variants of ochratoxin are known to naturally occur, only ochratoxin-A (OTA) and its non-chlorinated analogue, ochratoxin B (OTB) are found prevalently in food, animal feed, and beverages (Figure 1) [1,3]. Of these two ochratoxins, OTA is more toxic [1]. One approach to mitigate the health risks posed by OTA is to impose strict regulatory limits on the OTA levels in food matrices to control its bioaccumulation
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