An Quantum Calculation On The Binding Interaction Between The Iron Porphyrins And Odorant And Virtual Screening On Olfactory GPCR

ObjectiveHumans can discern and tens of thousands of different smell of memory, the sense of smell is also can only rely on subjective description language to distinguish between different smell. Odor identification can have objective indicators like the light and sound? Is there a link between the molecular structure of the compounds and odor characteristics? Hemoglobin is the most common metal protein in the body and how binding reaction between it and oxygen or nitric oxide or nitrogen? More and more odor molecules is proved to have a physiological role, and this kind of smell molecular targets but we have not known from these functions, whether this kind of odor molecules with the other targets?This study aims to research by quantum chemistry calculation how metal porphyrin rings and odor molecules binding reaction, and by using reverse virtual screening a series of odor molecules, explore the targets of such odor molecules, to study the mechanism of action of this kind of odor molecules and to explore its possible other role.Part One Selection and construction of odor moleculesBy collecting all kinds of odor molecules database about odor molecules in the description of the relevant data, a comprehensive database for odor molecules, and compares them according to a report in the previous literature content analysis, selected the body may be related to hemoglobin in referring to the common effect of odor molecules. To retrieve from the database correlation exists unknown mechanisms of odor molecules in the sense of smell GPCR targets virtual screening.Results Selected in the database and hemoglobin in metal porphyrin ring oxygen,nitric oxide and the nitrogen three kinds of odor molecules; From the database selected nerol, geraniol, nerol acetate and eugenol four kinds of odor molecules in the sense of smell of GPCR molecular targets virtual screening. Successful use the Chem Bio Office software construct the three-dimensional structure of the odor molecules.Part Two An Quantum Calculation on the Binding Interaction between the Iron porphyrins and OdorantIn order to study the combination of metal porphyrin rings and odor molecules,using semi-empirical quantum chemistry calculation software MOPAC2012 research hemoglobin iron porphyrins and three oxygen, nitric oxide and the nitrogen odor material effect, the combination of the basic institutions of the computing system parameters and the total energy change, and the determination of amino acids of ferrous ions surrounding the iron porphyrins, determine the amino acid in hemoglobin in combination with the effect of odor molecules, the quantum chemistry calculation to find the pattern of hemoglobin identification odor molecules research significance.Results Through comparing the PM7 algorithm and PM6 algorithm combined with the system and the parameters of the previous literature reports the experimental value can be concluded: PM7 precision and stability of the algorithm is significantly higher than PM6 algorithm; Through the calculation of the total energy of the whole system can be found, iron porphyrins when combined with oxygen molecules in the high spin state, is the minimum level of nitric oxide and the nitrogen molecule is the minimum level of low spin state. By comparing each amino acid in different systems of ferrous ion reaction, histidine 57, lysine 58 and leucine 61 can be found in the process of iron porphyrins combined with odor molecules play an important role.Part Three Virtual Screening on Olfactory GPCRTo investigate nerol, geraniol, nerol acetate and eugenol may function in the body of the targets, using molecular docking simulation software Surflex to reverse virtual screening of protein database, using the self-made script will filter the results score, the higher the score of the correlation between protein crystal and molecular docking is higher, the reverse virtual screening methods for odor molecules in the body targets research provides guidance significance.Results The top four nerol screening results are lipoyltransferase, complement inhibitor,deoxycytidylate deaminase and M17 leucyl aminopeptidase. The top four geraniol screening results are SAH nucleosidase, amidohydrolase and adenosine deaminase and carbonic anhydrase. The top four nerol acetate filter results are triazine hydrolase,tryptophan synthetase beta, tryptophan synthetase alpha and D-cysteine desulfhydrase;The top four eugenol screening results are beta lactamase, methane poison hydrogenase,tuberculosis salicylate synthase and quinoline t RNA genes transferase. Specific scoring list of results are shown in table 3 to table 6, filter the results target prediction and the effect of some literatures have been reported.Conclusions1 Semi-empirical quantum computing method PM7 algorithm is better than PM6 algorithm on precision value and stability.2 Iron porphyrins combined with oxygen molecule is the lowest level in the high spin state, combination of nitric oxide and the lowest energy level is low when nitrogen molecules spin state.3 Histidine 57, lysine58 and leucine 61 in iron porphyrins combined with odor molecules play an important role in the process.4 Virtual screening is a good way to the nerol, geraniol, nerol acetate and eugenol targets, and in line with the partial function of the literature.