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Toward computational risk assessment of nanoplastic impact on protein function: the case of vascular endothelial cadherin
Summary
Scientists used detailed computer simulations to study how tiny plastic particles (nanoplastics) might interfere with a protein that helps keep the walls of our blood vessels sealed and intact. They found that these plastic bits can weaken the bonds between cells lining blood vessels, potentially making them "leakier", and they built a tool to predict how this damage changes depending on the size of the plastic particle. This research is an early but important step toward understanding whether the nanoplastics increasingly found in our bodies could affect blood vessel health, though more studies are needed to confirm real-world impacts.
Micro-and nanoplastics are increasingly detected in ecological and biological systems. In various animals, there is growing evidence of nanoplastics impairing healthy development, reproduction, metabolism, etc. Nanoplastics have also been found in human organs. Still, the molecular mechanisms through which nanoplastics impact biomolecular function are insufficiently understood. Opportunely, computational techniques offer ways to unravel nanoplastic-biomolecule interactions. To advance such approaches, we use molecular dynamics (MD) simulations to understand a particular case of nanoplastic-induced protein disruption. Vascular endothelial (VE)-cadherin is a vital transmembrane junctional protein for the integrity of the endothelium, i.e., the inner lining of blood vessels. Via homotypic interactions, i.e., the extracellular domains of two proteins in neighboring cells bind to each other, VE-cadherins regulate endothelial permeability. Recently, experiments and simulations revealed that certain nanoplastics impair VE-cadherin adhesion, but computational cost and resolution prevented further investigation of the molecular process. By boosting MD simulations with enhanced sampling, we obtain high mechanistic detail and calculate dissociation free energies for VE-cadherin in the presence of nanoplastics of specific lengths. To enable scalable risk assessment, we also present a Bayesian exploration strategy to predict dissociation free energies as a function of nanoplastic length. Our pipeline holds promise for different nanopollutant-protein systems.