Determination of binding conformations of drugs to HAS and modeling of drug-HAS complex

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(1) It was carried out about the TRNOE measurement, the conformational analysis of binding drug (CAMDAS method, SUPERPOSE method etc.), contraction of the complex model by Flexi Dock method and molecular dynamics (MD) simulation of the complex model in the water solution.(2) Construction of complex models were carried out by docking (SYBYL Ver6.7: Tripos Co.) between binding conformations og drugs and HAS.I) Site I complex modelsIt could think about drugs which did binding at site I with hydrogen bond or electrostatic interaction between the part of negative charges of drugs and LYS199, ARG222, ARG257. It is found that benzen ring and alkyl group of drug forms hydrophobic interactions with PHE211, TRP214, PHE223, LEU238, ILE264, LEU276 and LEU290.II) Site II complex modelsThe electrostatic interactions between the part of negative charges and ARG410, TYR411 and ARG485 were suggested at the site II binding drugs. Furthermore, the part of hydrophobic of the drugs could think what fit did in hydrophobic pocket composed of VAL415, LEU423, LEU460 and PHE488 and so on.(3) Molecular dynamics (MD) simulation of complex modelsIt was suggested that the interaction (hydrogen bond, electrostatic and hydrophobic) shown with (2)-I) and (2)-II) were influence even in the water solution as a results of carrying out MD simulation about the constructed complex models (BMT354-site I and TLM53-site II) in the water.