Research Of The Interaction Between Small Molecular Drugs And Biological Macromolecular By Spectroscopic And Molecular Docking Methods

Biological macromolecule is the macromolecular substances in living organisms, and is the foundationof life substance. With the development of science and technology, more and more people give attention tothis matter. Biological macromolecules have become important research areas in modern biology,chemistry and medicine. Studies on supramolecular interactions of organic small molecular with biologicalmolecules have significantly contributed to the understanding of the structures and functions ofbiomacromolecules and some biophysical processes, and can obtain a lot of information of drug actions.In this dissertation, the study made by using the molecular spectroscopy, including UV-visible absorp--tion spectroscopy, fluorescence spectra and resonance light scattering spectra, combined with the mothodof the molecular simulation study are as follows:Describe briefly the important significance of the study on biological macromolecules, and summarizesome analysis methods used to analyze the interactions of biological macromolecules and drug smallmolecule, and their respective advantages and disadvantages.The interaction of pyrano [3,2-c] pyridine-5-ketone derivative and bovine serum albumin (BSA) isstudyed by spectroscopic method. The results of fluorescence and ultraviolet-visible absorption spectrashow that the pyrano [3,2-c] pyridine-5-ketone derivative leads mainly to fluorescence quenching ofbovine serum albumin by static process in the Tris-HCl buffer solution with pH=7.4physiologicalconditions. The main binding forces between them are hydrophobic interaction. The molecular dockingrevealed that the possible binding site of the derivative is bound in the large hydrophobic cavity ofsubdomain IIA.Under simulative physiological condition, the interaction between human serum albumin anduniconazole is studied by the fluorescence spectroscopy, ultraviolet-visible spectroscopy, sychronousfluorescence spectra and3-D fluorescence. Through the fluorescence spectra, fluorescence quenchingeffect of uniconazole to human serum albumin is found. The bonding points and constants at the differenttemperature are got. The interaction between uniconazole and human serum albumin is static quenching.The main forces of them are hydrogen bonding and van der Waals force. Uniconazole molecular is boundin the large hydrophobic cavity of subdomain â…¢A of human serum albumin by molecular simulation. By measuring the fluorescence spectrum of human serum albumin with tebuconazole, fluorescenceenhancement trends were found. The interaction mechanism was preliminary inferred by uv-vis absorptionspectra. The binding constant K value can be got. On the basis of the thermodynamic data,(â–³H) and (â–³S),the main binding force between them is electric attraction. The effect of tebuconazole on the conformationof HSA was analyzed by the synchronous and three-dimensional fluorescence spectroscopy. The result ofthe molecular modeling method showed the tebuconazole molecular is bound in the large hydrophobiccavity of subdomain â…¡ Aof human serum albumin.The interaction mechanism between benzimidazole derivatives, MTC, and DNA was studied undersimulative physiological condition. The interaction of MTC with DNA could cause a significantenhancement of fluorescence intensity, the hypochromic effect, red shift and isoabsorptive point ofabsorption spectra, indicating that there is an inserting interaction between MTC and DNA. The results ofpolarization, viscosity, salt effects, and electrochemical experiments showed that the electrostatic attractionbetween MTC and the bases of DNA provides the dominant driving force in the binding. Therefore, theabove results confirmed that intercalation and electrostatic binding are the two major modes for interactionbetween MTC and DNA in the Britton-Robinson buffer solution.