A New Method For Predicting Acute Toxicity Of Carbamate Pesticides Based On Human Serum Albumin Binding

Toxicity is one of the key factors that determine the success of drug development.The creation of new methods for early drug toxicity prediction is of great significance to drug development.In this article,we have established a new rapid and simple method,which based on binding information with carrier protein,for predicting the acute toxicity of carbamate pesticides.First,we have systematically clarified the binding information between carbamate pesticides and human serum albumin(HSA)through a series of methods including ultraviolet-visible spectra,fluorescence spectra,synchronous fluorescence spectra,three-dimensional fluorescence spectra,circular dichroism spectra and molecular docking technology.Then,a variety of toxicity prediction models were established to clarify the relationship between pesticide-HSA binding information and its acute toxicity.The main contents are shown as follows:Carbamate pesticides can bind with HSA and quench its fluorescence,which is a dynamic and static mixing quenching mechanism;although the number of binding sites between these pesticides and HSA is 1,there are different binding degrees between these pesticides and HSA;the calculation results of thermodynamic parameters showed that the main force between these pesticides and HSA was typical hydrophobic interaction;according to the theory of non-radiation energy transfer,it was determined that this kind of pesticide can bind with HSA and the binding distance was calculated.Synchronous fluorescence,three-dimensional fluorescence and circular dichroism spectra showed that it made a weak effect on the conformation of HSA by the addition of these pesticides,which reduced the content of α-helix.This article clarified that pesticide-HSA binding information was related to its acute toxicity,and based on the back-propagation neural network(BP-NN)algorithm,the model for predicting acute toxicity of carbamate pesticides was established;it is proposed and proved that it is practicable to predict drug toxicity based on the new perspective of binding with carrier protein;a relatively universal new method for acute toxicity of drugs has been established,namely the "Carrier protein binding information-toxicity relationship"(CPBITR).This method is suitable for the toxicity prediction of most drugs and has the advantages of wide application,simple and fast,etc.;and we established the "Platform for Predicting Drug Toxicity Based on the Information of Binding with Carrier Protein"(2021SR0226101).The new methods and new platforms for drug toxicity prediction established in this article have universal value.Other new models for drug toxicity prediction can be established according to our ideas and methods,which has an important supporting role for drug research and development.