Study On The Interaction Of Biologic Molecules And DNA By Chemical Information

The study of metal compounds and antibiotics (target molecules) as anti-cancer drug was a meaning and remarkable topics. The interaction of these target molecules and DNA was always a foucs that people paied close attention to. An understanding of how molecules bind to DNA would be potentially useful in the design and filtering new drugs, medicine synthesizes therapy and genetic diseases, etc.The binding mode, function mechanism, binding site point and binding constant are the main contents of these kinds of study. Up to now, fluorescence spectrum, ultraviolet-visible spectroscopy, capillary electrophoresis and electrochemical techniques have been developed for the identification and characterization of interactions between them, and have made great progress. However, there are still some problems in this field. First, it is difficult to find the influencing factors from the structure of molecules. Second, for batches of unknown molecules, it is difficult to predict the interaction from the experimental results.In this paper, principal components analysis, multivariate analysis, artificial neural network and hierarchical cluster analysis were applied to study the interaction of target molecules and DNA and their influencing factors.The main works of this paper-were as follows:Part I: IntroductionThis part related the developing history of chemical pattern recognition techniques (principal components analysis, artificial nerves net and hierarchical cluster analysis), introduced their basic mathematical theory and summed up their application in the field of analytical chemistry. Part II: Predictive studies on interaction between DNA and metal compoundsThe study of the interaction of metal compounds and DNA has very high theories worth and practical value. The way and the mechanism of the interaction of DNA and metal compound, and their general regulation were very useful to investigate the application of compound in anti-tumor medicine, molecular biology, technique and other related field of the living creature engineering.In this paper, 63 metal compounds were selected as research object to discuss main influencing factors of their interaction with DNA from molecular structure. Principal components analysis (PCA) was employed in order to reduce dimensionality and investigate which subset of variables could be more effective for classifying the compound according to their binding mode with DNA. Artificial nerves net (ANN) and multivariate analysis (MLR) were applied to establish two predicting constant models and one predicting binding mode model. 21 parameters (descriptors) that can influence the interaction of selected metal compound and DNA have been investigated. Results of the PCA study showed that there are 10 descriptors closely related to the interaction. The proposed models had the good accuracy in predicting constant and mode.Part III: Studies on the interaction between antibiotics and DNAInteraction between antibiotic molecules and DNA has the important significance on understanding drug function, designing molecular and filtering drugs. The present studies aimed to find interaction mechanism by experimental techniques. But it is difficult to find the structure influence factors that affect the interaction, and for batches of target molecular, the interaction information is difficult to predict.In this study, based on experimental data and quantified structure data, principal components analysis, ANN, HCA and MLR were applied to study the interaction. The influence factors were investigated. Two models of predicting interaction constant and one model of predicting interaction mode were established. Among 24 quantified parameters, it was found that there were 12 parameters that affected the interaction markedly. For the prediction of binding constant, the minimal relative error is only 0.17% (MLR) and 0.72% (ANN); for the prediction of binding mode (ANN), five test molecules are all consistent with experimental results.Part IV: Predict the interactive constant of DNA and heterocyclic molecules by modelAccording to the predictive constant model by previous studies, 30 binding constant of the interaction of heterocyclic molecules (dye compounds) and DNA were predicted in this study. Meanwhile, we discussed the effect of the interaction of target molecule by the influenced factors which had been found. The investigations in this work provide worthy information to design and filter medicine molecules.