Evaluation of Ochratoxin Recognition by Peptides Using Explicit Solvent Molecular Dynamics
Open Access
- 13 May 2017
- Vol. 9 (5), 164
- https://doi.org/10.3390/toxins9050164
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.Keywords
This publication has 46 references indexed in Scilit:
- Enhanced Sampling in Molecular Dynamics Using Metadynamics, Replica-Exchange, and Temperature-AccelerationEntropy, 2013
- Aptamers: A Promising Tool for Ochratoxin A Detection in Food AnalysisToxins, 2013
- Computational Design of Peptide Ligands for Ochratoxin AToxins, 2013
- ZINC: A Free Tool to Discover Chemistry for BiologyJournal of Chemical Information and Modeling, 2012
- Everything you wanted to know about Markov State Models but were afraid to askMethods, 2010
- Optimizing the Performance of Bias-Exchange Metadynamics: Folding a 48-Residue LysM Domain Using a Coarse-Grained ModelThe Journal of Physical Chemistry B, 2010
- PLUMED: A portable plugin for free-energy calculations with molecular dynamicsComputer Physics Communications, 2009
- The role of dynamic conformational ensembles in biomolecular recognitionNature Chemical Biology, 2009
- Binding of Small-Molecule Ligands to Proteins: “What You See” Is Not Always “What You Get”Structure, 2009
- VMD: Visual molecular dynamicsJournal of Molecular Graphics, 1996