The application of molecular dynamics simulations in mechanism of toxicity of organic contaminants

Abstract

Molecular dynamics (MD) simulations, an established statistical method based on Newtons equation of motion, are widely used for studying equilibria and dynamic properties of organic chemicals, materials and in particular biomacromolecular systems. Currently, MD simulations are frequently used to characterize interactions between various environmental contaminants and biomacromolecules. The binding mode of contaminants and conformational changes to target receptors induced by contaminant binding can be probed by MD simulations, and the mechanism of toxicity thus elucidated at the molecular level. The binding affinities of contaminants toward multiple target receptors can be evaluated by various binding free energy methods on the basis of trajectories produce from MD simulations. It is practical to virtually screen potential contaminants toward certain toxic end points, thereby facilitating rapid and high-throughput toxicity prediction and risk assessments. This review provides a basic introduction to the principles of MD simulations and MD software. The data preparation and MD operation are introduced in detail and key factors for MD simulations are described. Recent advances in MD simulations describing the interactions of contaminants with biomacromolecules are comprehensively discussed, and the interactions of organic contaminants with multiple transport proteins, target receptors and metabolic enzymes are highlighted. The perspective of future toxicity screening via MD simulations is provided for better risk assessment of environmental contaminants.