Study On Active Components Of Dense Bone Hit The Old Pill In The Treatment Of Osteoporosis

Objective: Using the software of computer aided drug design, accordingto the molecular docking method, on the basis of ligand and receptor "lock andkey principle", we can virtual screening on target enzymes which are closedwith osteoporosis and active components from dense bone hit the old pill. Tofind out the active components of dense bone hit the old pill and explore itschemical composition on osteoporosis for the purpose of treatments ofosteoporosis in clinical and modern development of traditional Chinesemedicine.Methods:.The application software comes from Accelrys company’sDiscovery Studio2.1(DS2.1).The compounds contained in dense bone hit theold pill decoction were chosen as objects of study. The molecular formulas ofthese compounds were collected from Traditional Chinese medicines:molecular structures，natural sources，and applications and Pharmacopoeia ofChina.More than530molecular formulas were collected totally. Drawing andtranslated into structure′s three-dimensional which can be used for moleculardocking through the ChemOffice software, and using DS2.1software inLigand Minimization interface,choosing MMFF force field optimization, wecan generate a small molecular library. The target enzyme structure which wasclosed with osteoporosis can be downloaded directly from the PDB library,there are five main, respectively estrogen receptor(ER), vitamin D receptor(VDR), peroxisome proliferators activated receptor gamma(PPARγ), cathespinK(CTSK) and carbonic anhydrase(CAⅡ). Download for DS2.1file formatsare available, and the protein three-dimensional structure model apart from itsstructure and the structure is not clear and water molecules, and eliminateendogenous ligand, then add hydrogen polarity, charge. Then choose theappropriate ligand binding pocket, five target enzyme activity of the pockets are pumped directly from the ligand-receptor complex structure. Usingmolecular docking process is the Discovery of Accelrys company Studiomolecular simulation software package, where the original body proteinmolecules as binding sites, all within the radius of0.5nm substructure asactive pocket part of the binding site. Ligand molecules in the pocket of thereceptor activity may be conformation mode Ligandfit module is adopted toimprove the collection.Then use flexible part of the series of commands todefine the small molecules, to set the parameters in ligandfit modulecompletes the docking, according to the interaction between ligand-targetenzyme energy size and geometric configuration matching degree is stronginteraction between the candidate compounds.Ligand each to create a newconformation, molecular docking between ligand and receptor.In Ligandfitcalculation,the biggest save conformation is set to100,and the otherparameters for Ligandfit given default values. Protein structure remain therigid when docking, application of monte carlo simulation to generate theligand molecular conformation,after each to create a new conformation of bothsmall molecules ligand and receptor protein, the docking between the scorecalculation.After sampling rigid molecules in the active site, optimization,optimization parameter is set to the steepest descent method. Dreiding forcefield. If molecular docking success, DOCKSCORE as evaluation index,prioritize, docking success compound DOCKSCORE and original body withprotein DOCKSCORE as threshold, it has collected more than530smallmolecule compounds in search of higher than the original bodyDOCKSCORE compounds. In this way, to highlight the dense bone hit the oldpill contains compounds are important target enzymes related to osteoporosismay be active.Results: In Ligandfit module,on the basis of energy complement eachother, complement each other and complementary principle such as chemicalenvironment, run the program to get their best DOCKSCORE. Compared withthe known original body dozen score,find the system and the ER, VDR, PPARgamma, CTSK, CA Ⅱfive target enzyme combined with good compounds respectively127,104,95,104,89, of which system respectively in the ER,VDR, PPAR gamma, CTSK, CAⅡ target enzyme combined with the higherscore of five compounds for icariin, psoralidin, physcion-8-O-β-D-glucopyran-oside, catalpol and ferulic acid. In these active small molecule compounds,including26molecules with three or more than three proteins have a stronginteraction, including icariin, naringin, aucubin, ecdysterone with four targetenzyme has good interaction. Medicinal indianmulberry root containscompounds and target enzyme score higher mainly anthraquinone compounds,as one of the active ingredients of medicinal indianmulberry root; Davalliamariesii contain compounds and target enzyme score higher mainly forrhizoma drynariae total flavonoids, as one of the main active components of it;Epimedium sagittatum contains compounds and target enzyme score highermainly for epimedium total flavonoids, the main active ingredients ofit.Malaytea scurfpea fruit contains compounds and target enzyme score highermainly coumarin and scurfpea fruit total flavonoids, the main activeingredients for it; Eucommia ulmoides Oliver contains compounds and targetenzyme score higher for the main part of the dilute ether terpenoids as one ofthe active ingredients of it; Achyranthes contain compounds and target enzymescore higher, mainly for steroid ketones is one of the active ingredient incultured; Fracture of the compounds and target enzyme score higher mainlytriterpenoid saponins and dilute ether terpenoids, as one of the activecomponents of radix dipsaci.Conclusion: Dense bone hit the old pill with ER, VDR, PPAR gamma,CTSK, CAⅡ five target enzyme combined with good active small moleculecompounds respectively127,104,95,98and89, including26molecules withthree or more than three proteins there were strong interaction, includingicariin, naringin, kaempferol, aucubin, ecdysterone with four target enzymehas good interaction. This shows that in these proteins associated withosteoporosis may have similar area, perform similar functions, thesemolecules are likely in regulating the activity of these proteins and proteininteraction has a very important role. These compounds may be dense bone hit the old pill play important active ingredients in the treatment of osteoporosis.In addition these molecular targeted a number of proteins at the same time,this is what the characteristics of traditional Chinese medicine, namely itseffectiveness composition way and targets, directly or indirectly, pathologicaland physiological process of different effects on the human body, resulting in acomprehensive effect. For the most part these active small moleculecompounds from traditional Chinese medicine like medicinal indianmulberryroot, davallia mariesii, epimedium sagittatum, malaytea scurfpea fruit,eucommia ulmoides oliver, achyranthes bidentata, himalayan teasel root,cornus officinalis, prepared rhizome of adhesive rehmannia, barbary wolfberryfruit, fructus broussonetiae, nagaimo, the smell of drugs into the kidneymeridian, with kidney strong bone, the effect of treating lumbar debility, alsoconfirmed from the side starting from the theory of kidney advocate bonemarrow feasibility for the treatment of osteoporosis.