Abstract
The current molecular docking study provided the Free Energy of Binding (FEB) for the interaction (nanotoxicity) between VDAC mitochondrial channels of three species (VDAC1-Mus musculus, VDAC1-Homo sapiens, VDAC2-Danio rerio) with SWCNT-H, SWCNT-OH, SWCNT-COOH carbon nanotubes. The general results showed that the FEB values were statistically more negative (p < 0.05) in the following order: (SWCNT-VDAC2-Danio rerio) > (SWCNT-VDAC1-Mus musculus) > (SWCNT-VDAC1-Homo sapiens) > (ATP-VDAC). More negative FEB values for SWCNT-COOH and OH were found in VDAC2-Danio rerio when compared with VDAC1-Mus musculus and VDAC1-Homo sapiens (p < 0.05). In addition, a significant correlation (0.66 > r2 > 0.97) was observed between n-Hamada index and VDAC nanotoxicity (or FEB) for the zigzag topologies of SWCNT-COOH and SWCNT-OH. Predictive Nanoparticles-Quantitative-Structure Binding-Relationship models (nano-QSBR) for strong and weak SWCNT-VDAC docking interactions were performed using Perturbation Theory, regression and classification models. Thus, 405 SWCNT-VDAC interactions were predicted using a nano-PT-QSBR classifications model with high accuracy, specificity, and sensitivity (73–98%) in training and validation series, and a maximum AUROC value of 0.978. In addition, the best regression model was obtained with Random Forest (R2 of 0.833, RMSE of 0.0844), suggesting an excellent potential to predict SWCNT-VDAC channel nanotoxicity. All study data are available at https://doi.org/10.6084/m9.figshare.4802320.v2.
Highlights
The current molecular docking study provided the Free Energy of Binding (FEB) for the interaction between voltage-dependent anion channel (VDAC) mitochondrial channels of three species (VDAC1-Mus musculus, VDAC1Homo sapiens, VDAC2-Danio rerio) with single-walled carbon nanotubes (SWCNT)-H, SWCNT-OH, SWCNT-COOH carbon nanotubes
After docking studies we developed a new Perturbation Theory (PT)-NQSBR model using as input SWCNT-structural properties (Hamada indices, etc.) and Free Energy of Binding (FEB values), obtained after Docking Simulation (DS) to perform a PT-NQSBR model based on Linear Discriminant Analysis (LDA) technique
The results showed that the affinity was statistically more negative for FEB values following the order (SWCNT-VDAC2-Danio rerio) > (SWCNT-VDAC1-Mus musculus > (SWCNT-VDAC1-Homo sapiens) ≈ (ATP-VDAC)
Summary
The current molecular docking study provided the Free Energy of Binding (FEB) for the interaction (nanotoxicity) between VDAC mitochondrial channels of three species (VDAC1-Mus musculus, VDAC1Homo sapiens, VDAC2-Danio rerio) with SWCNT-H, SWCNT-OH, SWCNT-COOH carbon nanotubes. Single-walled carbon nanotubes (SWCNT) have rapidly become one of the most widely studied nanomaterials, based on their unique physico-chemical properties that allow their potential use in new nanomedicine applications like pharmaceutical excipients for the design of several drug delivery systems[10,11]. The VDAC channel inhibition by SWCNT could be an attractive therapeutic strategy to induce mitotoxicity based on specific VDAC-modulation Following this idea, the chemo-informatics tools based on Docking Simulation (DS)[12] appears to be an efficient strategy for the potential nanotoxicity prediction and SWCNT environmental impact. Several in vitro studies have demonstrated that SWCNTs exert their cytotoxicity mechanism after their accumulation in the mitochondria matrix[16,17]
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