Calorimetry And Molecular Simulation Studied On The Interaction Between Protein With Small Drug And Analogsmolecules

Protein is a kind of important macromolecule which takes part in a variety of physiological activities in biological body. Some biological molecules whether endogenous substance or exogenous material can react with proteins then affect the metabolism of the body. The study of interaction between proteins and small molecular structure analogues helps to understand the absorption, distribution, metabolism, excretion and so on of small molecules in the body. Furthermore, it also provides ideas for researchers to design and development drugs and helps to screen out high efficacy and low toxic drugs, which is hot topic in nowadays.Alkaloids, oxazoles and pyrazoles are all have effectiveness of antisepsis, antiphlogosis and analgesia. It is significant for pharmacology, pharmacodynamics and toxicology to study the binding between them. This thesis proceeded innovative research based on the results of other researchers, comprehensive utilize of isothermal titration calorimetry and molecular simulation to study certain small molecules and human serum albumin interactions. This paper includes the following sections: Chapter 1: It introduced the structures, functions and natures of human serum album and summarized the significance, progress and techniques of the binding between protein and small molecules. Moreover, the theory and operation method of ITC and molecular simulation also been summarized. Chapter 2: This experiment screened out theophylline and caffeine from 4 kinds of alkaloid by ITC. Then investigated the influence for the interaction at different conditions combined with molecular simulation. The result showed that the binding constants are almost no difference between theophylline and caffeine and hydrophobic interaction is the main reason for the combination. Chapter 3: This chapter took HSA and 16 kinds of oxazole class structure analogues as research objects, comprehensive utilized of ITC and molecular simulation for the research. It showed that YZ-1i and YZ-1u are bioactivity and the binding constant of YZ-1u is bigger. The results of molecular simulation showed that different moleculars have different binding sites with HSA which conforms to the study of calorimetry. Chapter 4: Study of the interaction between HSA and 18 kinds of parazole class structure analogues by ITC and molecular simulation. We know that there are 5 kinds of parazole class structure analogues which take interaction with HSA and the binding constants arrange from big to small in order is ZXT-1c>ZXT-1a>ZXT-1e>ZXT-1b>ZXT-1j. In addition, hydrophobic interaction plays an importent role in all systerm. But hydrogen bond and Van der Waals force have a certain degree of influence for the interaction, especially in the interaction between HSA and ZXT-1a、ZXT-1b 、ZXT-1e. The results of molecular simulation are close to that obtained by calorimetry experimental method.