Molecular Dynamics Study On The Interaction Mechanism Of Single-walled Carbon Nanotubes With Two Typical Proteins

Nanomaterials have attracted wide attention due to their special physicochemical properties.However,a number of studies in recent years have demonstrated that nanomaterials have potential toxicity,which may cause pulmonary toxicity,reproductive toxicity,cardio toxicity,and neurotoxicity when they entering the body.Therefore,it is paramount importance to unravel the structural details of interactions between nanoparticles and biological systems at the molecular level,aiming to reveal the potential adverse biological impacts.As a typical representative of nanomaterials,single-walled carbon nanotubes(SWCNT)have been widely used in science and technology due to their novel physicochemical properties.SWCNT can enter the body through different pathways and then bind to various proteins in the body,which leads to its possible toxicological effects on the body.In this paper,we selected bovine serum albumin(BSA)and estrogen receptor alpha(ER?)as model proteins to study their interaction mechanism with SWCNT by animals experiments,spectroscopic experiments,and molecular dynamics simulations.This work has certain reference value for us to understand the mechanism of SWCNT with other biological macromolecules.In the second part of this paper,we explored the interaction mode between BSA and SWCNT through spectroscopic experiments and molecular dynamics simulations.BSA is the most abundant protein in serum,which can bind various exogenous compounds.Fluorescence quenching experiments and competitive displacement experiments demonstrated that SWCNT can bind to BSA and their binding sites are located in the subdomain IB;Thermodynamic experiments and circular dichroism analysis showed that the interaction between SWCNT and BSA was dominated by hydrophobic interaction,the quenching mechanism of SWCNTs on BSA was static quenching,and the combination of SWCNT resulted in a conformational change in secondary structure levels.Molecular dynamics simulations further demonstrated that hydrophobic interactions are the main driving force for the binding behavior.The binding free energy calculations further demonstrated that the binding sites of SWCNT are located in the subdomain IB.Residue network analysis shows that the combination of SWCNT changed the residue interaction network near the binding cavity,which led to a conformational change both at secondary and tertiary structure levels.In the third part of this paper,we studied the interaction mechanism between SWCNT and ER? through animals experiments,spectroscopic experiments and molecular dynamics simulations.The estrogen receptor is one of the members of the nuclear receptor superfamily,it is an important component which affects the development and function of the reproductive system.The Interaction with SWCNT may lead to reproductive toxicity.Therefore,we demonstrated that single-walled nanotubes(SWCNTs)can bind to estrogen receptor ?(ER?)through fluorescence quenching experiments;The estradiol levels in rat serum analysis and Western Blot analysis demonstrated that low-dose exposure of single-walled nanotubes(SWCNTs)in rats resulted in a increasing level of estradiols in rats serum and a decreasing expression of ER? in uterus,which demonstrates that SWCNT may have estrogen-interfering effects.At the same time,molecular dynamics simulations have demonstrated that SWCNT has strong binding affinity to ER?,and their binding destroyed the residue interaction network of ER?,especially the destruction to the hydrogen bond network,which led to a conformational change at secondary structure levels of ER?.From the above conclusions,we can infer that single-walled nanotubes have potentially toxicity to the estrogen receptor ER?,affect its natural activity,and may cause disorders and disorders related to the body's function.