{"id":968,"date":"2020-02-07T13:15:35","date_gmt":"2020-02-07T04:15:35","guid":{"rendered":"https:\/\/www.insilico.jp\/blog\/?p=968"},"modified":"2022-02-22T14:50:18","modified_gmt":"2022-02-22T05:50:18","slug":"sirt1_ligand","status":"publish","type":"post","link":"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/","title":{"rendered":"\u8ad6\u6587\u7d39\u4ecb\uff08SIRT1\u6d3b\u6027\u5316\u5408\u7269\u306e\u63a2\u7d22\uff09"},"content":{"rendered":"\n

\u3000\u5b66\u751f\u30a2\u30eb\u30d0\u30a4\u30c8K\u3055\u3093\u306eLigandScout\u95a2\u9023\u8ad6\u6587\u306e\u7d39\u4ecb\u8a18\u4e8b\u3067\u3059\uff0eLigandScout\u306e\u6d3b\u7528\u4e8b\u4f8b\u3068\u3057\u3066\u3054\u53c2\u8003\u306b\u306a\u308c\u3070\u5e78\u3044\u3067\u3059\uff0e<\/p>\n\n\n\n

\uff08\u4ee5\u4e0b\uff0c\u8ad6\u6587\u7d39\u4ecb\u8a18\u4e8b\uff09<\/p>\n\n\n\n

\u672c\u8a18\u4e8b\u3067\u306f\u3001\u6b21\u306e\u8ad6\u6587\u3092\u3001LigandScout\u306e\u5229\u7528\u3092\u4e2d\u5fc3\u306b\u7d39\u4ecb\u3057\u307e\u3059\u3002<\/p>\n\n\n\n

In silico and in vitro identification of candidate SIRT1 activators from Indonesian medicinal plants compounds database
\uff08Azminah Azminah, Linda Erlinac, Maksum Radji, Abdul Mun\u2019ia, Rezi Riadhi Syahdi, Arry Yanuar, Computational Biology and Chemistry<\/em> Volume 83, December 2019, 107096\uff09 <\/p>\n\n\n\n

https:\/\/doi.org\/10.1016\/j.compbiolchem.2019.107096<\/a><\/p>\n\n\n\n

\u30b5\u30fc\u30c1\u30e5\u30a4\u30f3\uff08Sirtuin\uff09\u306f\u3001\u30af\u30e9\u30b9III\u30d2\u30b9\u30c8\u30f3\u8131\u30a2\u30bb\u30c1\u30eb\u5316\u9175\u7d20\u3067\u3042\u308a\u3001NAD+\u4f9d\u5b58\u6027\u8131\u30a2\u30bb\u30c1\u30eb\u5316\u9175\u7d20\u7fa4\u306e\u7dcf\u79f0\u3067\u3059\u3002\u305d\u306e\u4e2d\u306e\u4e00\u3064\u30b5\u30fc\u30c1\u30e5\u30a4\u30f31\uff08SIRT1\uff09\u306e\u6d3b\u6027\u5316\u5408\u7269\u306f\u30012\u578b\u7cd6\u5c3f\u75c5\u3001\u8001\u5316\u30d7\u30ed\u30bb\u30b9\u7b49\u306b\u5bfe\u3057\u3066\u4fdd\u8b77\u7684\u306a\u5f79\u5272\u3092\u679c\u305f\u3057\u3066\u3044\u308b\u53ef\u80fd\u6027\u304c\u793a\u5506\u3055\u308c\u3066\u3044\u307e\u3059\u3002\u8457\u8005\u3089\u306f\u3001\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u624b\u6cd5\u306b\u57fa\u3065\u304f\u30d0\u30fc\u30c1\u30e3\u30eb\u30b9\u30af\u30ea\u30fc\u30cb\u30f3\u30b0\u306b\u3088\u308a\u3001\u30a4\u30f3\u30c9\u30cd\u30b7\u30a2\u306e\u85ac\u8349\u306b\u542b\u307e\u308c\u308b1377\u500b\u306e\u5316\u5408\u7269\u306e\u4e2d\u304b\u3089\u30b5\u30fc\u30c1\u30e5\u30a4\u30f3\u6d3b\u6027\u5316\u5408\u7269\u3068\u306a\u308a\u5f97\u308b4\u500b\u306e\u5316\u5408\u7269\u3092\u898b\u51fa\u3057\u307e\u3057\u305f\u3002<\/p>\n\n\n\n

\u672c\u8ad6\u6587\u306b\u304a\u3051\u308b\u89e3\u6790\u624b\u9806\u306f\u4e0b\u56f3\u306e\u901a\u308a\u3067\u3059\uff08Graphical abstract<\/strong>\uff09\u3002<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Graphical abstract<\/strong><\/p>\n\n\n\n\n\n\n\n

\u5316\u5408\u7269\u63a2\u7d22<\/h1>\n\n\n\n

\u5019\u88dc\u5316\u5408\u7269\u306e\u63a2\u7d22\u306b\u306f\u3001Pharmacophore-Based Virtual Screening\u304c\u63a1\u7528\u3055\u308c\u3066\u304a\u308a\u3001LigandScout 4.2\u304c\u4f7f\u7528\u3055\u308c\u3066\u3044\u307e\u3059\u3002LigandScout\u3067\u306f\u3001\u69cb\u9020\u30d9\u30fc\u30b9\u3068\u30ea\u30ac\u30f3\u30c9\u30d9\u30fc\u30b9\u306e2\u3064\u306e\u624b\u6cd5\u304b\u3089\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u30e2\u30c7\u30eb\u306e\u4f5c\u6210\u304c\u53ef\u80fd\u3067\u3059\u3002\u69cb\u9020\u30d9\u30fc\u30b9\u30e2\u30c7\u30eb\u306f\u3001\u30d2\u30c8SIRT1\u306ePDB\u30d5\u30a1\u30a4\u30eb\uff08PDBID\uff1a4ZZJ\uff09\u306e\u30a2\u30ed\u30b9\u30c6\u30a3\u30c3\u30af\u7d50\u5408\u90e8\u4f4d\u304b\u3089\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u3092\u4f5c\u6210\u3057\u3066\u3044\u307e\u3059 \uff08Fig. 2<\/strong>\uff09 \u3002\u30ea\u30ac\u30f3\u30c9\u30d9\u30fc\u30b9\u30e2\u30c7\u30eb\u306f\u3001\u65e2\u77e5\u306e\u30b5\u30fc\u30c1\u30e5\u30a4\u30f3\u6d3b\u6027\u5316\u5408\u7269\u3092\u300112\u500b\u306e\u30c8\u30ec\u30fc\u30cb\u30f3\u30b0\u30bb\u30c3\u30c8\u306825\u500b\u306e\u30c6\u30b9\u30c8\u30bb\u30c3\u30c8\u306b\u5206\u3051\u3066\u3001\u524d\u8005\u3092\u7528\u3044\u306610\u500b\u306e\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u30e2\u30c7\u30eb\u3092\u69cb\u7bc9\u3057\u3066\u3044\u307e\u3059\u3002\u305d\u306e\u5f8c\u3001\u69cb\u9020\u30d9\u30fc\u30b9\u3068\u30ea\u30ac\u30f3\u30c9\u30d9\u30fc\u30b9\u3001\u4e21\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u30e2\u30c7\u30eb\u306e\u30d0\u30ea\u30c7\u30fc\u30b7\u30e7\u30f3\u304c\u884c\u308f\u308c\u3066\u3044\u307e\u3059\u3002LigandScout\u3067\u306f\u3001\u6d3b\u6027\u5316\u5408\u7269\u53ca\u3073\u30c7\u30b3\u30a4\u5316\u5408\u7269\u3092\u7528\u3044\u3066\u30b9\u30af\u30ea\u30fc\u30cb\u30f3\u30b0\u3092\u884c\u3046\u3053\u3068\u3067\u3001\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u30e2\u30c7\u30eb\u306e\u6027\u80fd\u6307\u6a19\u3068\u306a\u308b\u30d1\u30e9\u30e1\u30fc\u30bf\uff08sensitivity, specificity, accuracy, receiver operating characteristic (ROC), areas under the curves (AUC\uff1a1,5,10,100%), enrichment factors (EF\uff1a1,5,10,100%)\uff09\u3092\u6c42\u3081\u308b\u3053\u3068\u304c\u3067\u304d\u307e\u3059\u3002\u7b46\u8005\u3089\u306f\u3001\u30c6\u30b9\u30c8\u30bb\u30c3\u30c8\u3068\u3057\u305f\u65e2\u77e5\u306e\u30b5\u30fc\u30c1\u30e5\u30a4\u30f3\u6d3b\u6027\u5316\u5408\u726925\u500b\u3068Directory of Useful Decoys : Enhanced (http:\/\/dude.docking.org\/generate)\u3092\u7528\u3044\u3066\u4f5c\u6210\u3057\u305f\u30c7\u30b3\u30a4\u5316\u5408\u72691392\u500b\u3092\u7528\u3044\u3066\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u30e2\u30c7\u30eb\u306e\u8a55\u4fa1\u3068\u30ea\u30d5\u30a1\u30a4\u30f3\u30e1\u30f3\u30c8\u3092\u884c\u3063\u3066\u3044\u307e\u3059\u3002\u3053\u306e\u7d50\u679c\u3001\u69cb\u9020\u30d9\u30fc\u30b9\u306f\u6761\u4ef6\uff08AUC1,5,10,100%<\/sub>\u5168\u30660.5\u3088\u308a\u5927\u3001\u304b\u3064EF1,5,10,100%<\/sub>\u5168\u30661\u3088\u308a\u5927\uff09\u3092\u6e80\u305f\u3057\u305f\u305f\u3081\u3001\u305d\u306e\u307e\u307e\u63a1\u7528\u3001\u307e\u305f\u30ea\u30ac\u30f3\u30c9\u30d9\u30fc\u30b9\u30e2\u30c7\u30eb\u3067\u306f\u6700\u3082\u6027\u80fd\u306e\u3088\u304b\u3063\u305fModel 1\u3092\u63a1\u7528\u3057\u3066\u3044\u307e\u3059 \uff08Fig. 3<\/strong>\uff09 \u3002<\/p>\n\n\n\n

\u305d\u306e\u5f8c\u3001\u69cb\u9020\u30d9\u30fc\u30b9\u3068\u30ea\u30ac\u30f3\u30c9\u30d9\u30fc\u30b92\u3064\u306e\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u3092\u30af\u30a8\u30ea\u3068\u3057\u30661377\u500b\u306e\u85ac\u8349\u5316\u5408\u7269\u30c7\u30fc\u30bf\u30d9\u30fc\u30b9\u3092\u5bfe\u8c61\u3068\u3057\u305f\u30d0\u30fc\u30c1\u30e3\u30eb\u30b9\u30af\u30ea\u30fc\u30cb\u30f3\u30b0\u304c\u5b9f\u65bd\u3055\u308c\u3066\u3044\u307e\u3059\u3002\u69cb\u9020\u30d9\u30fc\u30b9\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u30e2\u30c7\u30eb\u304b\u3089\u306f10\u500b\u3001\u30ea\u30ac\u30f3\u30c9\u30d9\u30fc\u30b9\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u30e2\u30c7\u30eb\u304b\u3089\u306f18\u500b\u306e\u5316\u5408\u7269\u304c\u30d2\u30c3\u30c8\u5316\u5408\u7269\u3068\u3057\u3066\u5f97\u3089\u308c\u307e\u3057\u305f\u3002<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Fig. 2.<\/strong> LigandScout\u306b\u3088\u308a\u4f5c\u6210\u3055\u308c\u305f\u69cb\u9020\u30d9\u30fc\u30b9\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2 (a) SIRT1 (b) 3D\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2 (c) \u5171\u7d50\u6676\u5316\u3055\u308c\u305f4TQ\u30ea\u30ac\u30f3\u30c9\u306e\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u8981\u7d20\uff08HI1\/HI2\/HI3\/HI4:\u758e\u6c34\u6027\u76f8\u4e92\u4f5c\u7528\uff0cHBA:\u6c34\u7d20\u7d50\u5408\u53d7\u5bb9\u4f53\uff09\u3068\u8ddd\u96e2<\/p>\n\n\n\n

Table 1.<\/strong> \u30ea\u30ac\u30f3\u30c9\u30d9\u30fc\u30b9\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u30e2\u30c7\u30eb\uff08Model 1-10\uff09\u306e\u66f2\u7dda\u4e0b\u9762\u7a4d\uff08AUC\uff09\u3068\u6fc3\u7e2e\u4fc2\u6570\uff08EF\uff09\u3001Sensitivity\u3001Specificity\u3001Accuracy<\/p>\n\n\n\n

\n Model<\/strong>\n <\/td>\n AUC100%<\/strong>\n <\/td>\n EF1%<\/strong>\n <\/td>\n Sensitivity<\/strong>\n <\/td>\n Specificity<\/strong>\n <\/td>\n Accuracy%<\/strong>\n <\/td><\/tr>
\n 1<\/strong>\n <\/td>\n 0.88\n <\/td>\n 12.1\n <\/td>\n 0.84\n <\/td>\n 0.91\n <\/td>\n 91.1\n <\/td><\/tr>
\n 2<\/strong>\n <\/td>\n 0.86\n <\/td>\n 8.1\n <\/td>\n 0.80\n <\/td>\n 0.91\n <\/td>\n 90.8\n <\/td><\/tr>
\n 3<\/strong>\n <\/td>\n 0.84\n <\/td>\n 12.1\n <\/td>\n 0.92\n <\/td>\n 0.63\n <\/td>\n 63\n <\/td><\/tr>
\n 4<\/strong>\n <\/td>\n 0.90\n <\/td>\n 16.2\n <\/td>\n 0.96\n <\/td>\n 0.60\n <\/td>\n 61\n <\/td><\/tr>
\n 5<\/strong>\n <\/td>\n 0.76\n <\/td>\n 0.0\n <\/td>\n 0.96\n <\/td>\n 0.47\n <\/td>\n 48\n <\/td><\/tr>
\n 6<\/strong>\n <\/td>\n 0.88\n <\/td>\n 16.2\n <\/td>\n 0.96\n <\/td>\n 0.58\n <\/td>\n 58\n <\/td><\/tr>
\n 7<\/strong>\n <\/td>\n 0.90\n <\/td>\n 16.2\n <\/td>\n 1.00\n <\/td>\n 0.44\n <\/td>\n 45\n <\/td><\/tr>
\n 8<\/strong>\n <\/td>\n 0.78\n <\/td>\n 20.2\n <\/td>\n 0.92\n <\/td>\n 0.62\n <\/td>\n 60\n <\/td><\/tr>
\n 9<\/strong>\n <\/td>\n 0.79\n <\/td>\n 16.2\n <\/td>\n 0.92\n <\/td>\n 0.62\n <\/td>\n 65\n <\/td><\/tr>
\n 10<\/strong>\n <\/td>\n 0.92\n <\/td>\n 12.1\n <\/td>\n 1.00\n <\/td>\n 0.62\n <\/td>\n 46\n <\/td><\/tr><\/tbody><\/table><\/figure>\n\n\n\n

<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Fig. 3.<\/strong> \u30ea\u30ac\u30f3\u30c9\u30d9\u30fc\u30b9\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2 Model 1. \u69cb\u6210\u8981\u7d20\uff08HI1\/HI2:\u758e\u6c34\u6027\u76f8\u4e92\u4f5c\u7528\uff0cAR1\/AR2:\u82b3\u9999\u74b0\uff0c HBA:\u6c34\u7d20\u7d50\u5408\u53d7\u5bb9\u4f53\uff09\u3068\u8ddd\u96e2<\/p>\n\n\n\n

\u30d2\u30c3\u30c8\u5316\u5408\u7269\u306e\u7d5e\u308a\u8fbc\u307f<\/h1>\n\n\n\n

Pharmacophore-Based\nVirtual Screening\u306b\u3088\u308a\u5f97\u3089\u308c\u305f28\u500b\u306e\u30d2\u30c3\u30c8\u5316\u5408\u7269\u306b\u3001\u30ea\u30d4\u30f3\u30b9\u30ad\u30fc\u306e\u30eb\u30fc\u30eb\u30fb\u30aa\u30d6\u30fb\u30d5\u30a1\u30a4\u30d6\uff08molecular\nweight<500, HBA<10, HBD<5, clogP <5\uff09\u3092\u9069\u7528\u3057\u3001\u85ac\u5264\u5019\u88dc\u3068\u3057\u3066\u9069\u3057\u305f\u5316\u5408\u7269\u3092\u7d5e\u308a\u8fbc\u307f\u307e\u3057\u305f\u3002\u7d50\u679c\u3068\u3057\u3066\u3001\u69cb\u9020\u30d9\u30fc\u30b9\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u30e2\u30c7\u30eb\u306b\u3088\u308b\u30d2\u30c3\u30c8\u5316\u5408\u7269\u304b\u3089\u306f1\u500b\uff08Mulberrin\uff09\u3001\u30ea\u30ac\u30f3\u30c9\u30d9\u30fc\u30b9\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u30e2\u30c7\u30eb\u306b\u3088\u308b\u30d2\u30c3\u30c8\u5316\u5408\u7269\u304b\u3089\u306f3\u500b\uff08Quinine\u3001Quinidine\u3001Gartanin\uff09\u3001\u8a084\u500b\u306e\u5316\u5408\u7269\u304c\u7d5e\u308a\u8fbc\u307e\u308c\u3066\u3044\u307e\u3059\u3002<\/p>\n\n\n\n

\u30d2\u30c3\u30c8\u5316\u5408\u7269\u306e\u8a55\u4fa1<\/h1>\n\n\n\n

\u7d9a\u3044\u3066\u3001\u7406\u8ad6\u8a08\u7b97\u3068\u5b9f\u9a13\u306e\u53cc\u65b9\u304b\u3089\u3001\u7d5e\u308a\u8fbc\u3093\u30604\u500b\u306e\u5019\u88dc\u5316\u5408\u7269\u306e\u30b5\u30fc\u30c1\u30e5\u30a4\u30f3\u6d3b\u6027\u5316\u5408\u7269\u3068\u3057\u3066\u306e\u9069\u6027\u304c\u8a55\u4fa1\u3055\u308c\u3066\u3044\u307e\u3059\u3002<\/p>\n\n\n\n

\u7406\u8ad6\u8a08\u7b97\u3067\u306f\u3001SIRT1\u3068\u306e\u30c9\u30c3\u30ad\u30f3\u30b0\u8a08\u7b97\u53ca\u3073MD\u8a08\u7b97\u304c\u884c\u308f\u308c\u3066\u3044\u307e\u3059\u3002\u30c9\u30c3\u30ad\u30f3\u30b0\u8a08\u7b97\u306b\u306fAutoDock4Zn\uff08http:\/\/autodock.scripps.edu\/resources\/autodockzn-forcefield\uff09\u304c\u5229\u7528\u3055\u308c\u3066\u304a\u308a\u3001PDB:4ZZJ\u306e\u30ea\u30ac\u30f3\u30c9\u3067\u3042\u308b4TQ\u3068\u30b9\u30af\u30ea\u30fc\u30cb\u30f3\u30b0\u3067\u5f97\u3089\u308c\u305f4\u500b\u306e\u5019\u88dc\u5316\u5408\u7269\u3068SIRT1\u3068\u306e\u30c9\u30c3\u30ad\u30f3\u30b0\u30dd\u30fc\u30ba\u53ca\u3073\u76f8\u4e92\u4f5c\u7528\u304c\u6bd4\u8f03\u3055\u308c\u3066\u3044\u307e\u3059\uff08Fig. 4<\/strong>\uff09\u3002Mulberrin\u3001Quinine\u3001Quinidine\u3001Gartanin\u306e\u30c9\u30c3\u30ad\u30f3\u30b0\u30b9\u30b3\u30a2\u306f\u3001\u305d\u308c\u305e\u308c-4.89\u3001-4.71\u3001-4.98\u3001-5.67 kcal\/mol\u3067\u3057\u305f\u3002\u307e\u305f\u6bd4\u8f03\u306e\u305f\u3081\u3001\u30b5\u30fc\u30c1\u30e5\u30a4\u30f3\u6d3b\u6027\u5316\u5408\u7269\u306e\u4e00\u3064\u3067\u3042\u308bResveratrol\u3068SIRT\u963b\u5bb3\u5264\u306eNicotinamide\u3082\u30c9\u30c3\u30ad\u30f3\u30b0\u8a08\u7b97\u3055\u308c\u3066\u304a\u308a\u3001\u5404\u30b9\u30b3\u30a2\u306f\u3001-4.29\u3001-4.63 kcal\/mol\u3067\u3057\u305f\u3002\u3053\u308c\u3089\u306e\u5316\u5408\u7269\u3068\u7d50\u5408\u90e8\u4f4d\u5468\u8fba\u306e\u30a2\u30df\u30ce\u9178\u6b8b\u57fa\u3068\u306e\u76f8\u4e92\u4f5c\u7528\u304cFig. 5<\/strong>\u306b\u793a\u3055\u308c\u3066\u3044\u307e\u3059\u3002<\/p>\n\n\n\n

MD\u8a08\u7b97\u306b\u306f\u3001Amber\uff08https:\/\/ambermd.org\/\uff09\u304c\u5229\u7528\u3055\u308c\u3066\u304a\u308a\u3001\u30c9\u30c3\u30ad\u30f3\u30b0\u3068\u540c\u69d8\u30014TQ\u30684\u3064\u306e\u5019\u88dc\u5316\u5408\u7269\u306b\u3064\u3044\u3066\u3001RMSD\u3068RMSF\u305d\u308c\u305e\u308c\u306e\u5024\u3001\u307e\u305f\u3001MM-GB(PB)SA\u6cd5\u306b\u3088\u3063\u3066\u0394G[kcal\/mol]\u304c\u6c42\u3081\u3089\u308c\u3066\u3044\u307e\u3059\uff08Fig. Extra 1<\/strong>\uff09\u3002<\/p>\n\n\n\n

in vitro<\/em>\u8a66\u9a13\u3067\u306f\u3001SIRT\u306e\u76f8\u5bfe\u7684\u306a\u9175\u7d20\u6d3b\u6027\u3092\u7cbe\u88fd\u9175\u7d20\u3088\u308a\u6e2c\u5b9a\u53ef\u80fd\u306a\u767a\u5149\u30a2\u30c3\u30bb\u30a4\u30b7\u30b9\u30c6\u30e0SIRT-Glo\u2122 Assays\u304c\u7528\u3044\u3089\u308c\u3066\u304a\u308a\u30014\u3064\u306e\u5019\u88dc\u5316\u5408\u7269\u306eEC50\u5024\u3092\u6c42\u3081\u3066\u3044\u307e\u3059\uff08Fig. 8<\/strong>\uff09\u3002<\/p>\n\n\n\n

<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Fig. 4.<\/strong> \u30c9\u30c3\u30ad\u30f3\u30b0\u7d50\u679c\u306b\u57fa\u3065\u304f\u76f8\u4e92\u4f5c\u7528\uff08\u3044\u305a\u308c\u3082LigandScout\u306b\u3088\u308a\u4f5c\u56f3\uff09(a)4ZZJ\u3068Mulberrin\u306e2D\u56f3 (b)Murberrin\u306e3D\u30b5\u30fc\u30d5\u30a7\u30b9\u56f3\uff08\u89aa\u6c34\u6027\uff1a\u9752\u8272\u3001\u758e\u6c34\u6027\uff1a\u7070\u8272\uff09 (c)Qunine (d)Quinidne (e)Gartanin\u54042D\u56f3<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Fig. 5.<\/strong> (1) \u5171\u7d50\u6676\u69cb\u9020\uff08PDB\uff1a4ZZJ\uff09\u306b\u304a\u3051\u308b4TQ\u30ea\u30ac\u30f3\u30c9\u3001\u4e26\u3073\u306b(2)Mulberrin\u3001 (3)Quinine\u3001(4)Quinidine\u3001(5)Gartanin\u3001(6)Resveratrol\u3001(7)Nicotinamide\u306e\u5404\u30c9\u30c3\u30ad\u30f3\u30b0\u7d50\u679c\u306b\u57fa\u3065\u304fSIRT1\u30a2\u30ed\u30b9\u30c6\u30ea\u30c3\u30af\u30b5\u30a4\u30c8\u306e\u30a2\u30df\u30ce\u9178\u6b8b\u57fa\u3068\u306e\u76f8\u4e92\u4f5c\u7528<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Fig. Extra 1.<\/strong> MM-GB(PB)SA\u6cd5\u306b\u3088\u308b\u7d50\u5408\u81ea\u7531\u30a8\u30cd\u30eb\u30ae\u30fc\u0394G\u5909\u5316\uff08\u8ad6\u6587Table 2\u306b\u57fa\u3065\u304d\u30b0\u30e9\u30d5\u5316\uff09<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Fig. 8.<\/strong> Mulberrin, Quinine, Quinidine, Gartanin\u306e\u6d3b\u6027\u30d7\u30ed\u30d5\u30a1\u30a4\u30eb\uff08SIRT-Glo\u2122\uff09<\/p>\n\n\n\n

\u7d50\u8ad6<\/h1>\n\n\n\n

\u30a4\u30f3\u30c9\u30cd\u30b7\u30a2\u306e\u85ac\u8349\u5316\u5408\u72691377\u500b\u3092\u5bfe\u8c61\u3068\u3057\u305f\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u306b\u57fa\u3065\u304f\u30d0\u30fc\u30c1\u30e3\u30eb\u30b9\u30af\u30ea\u30fc\u30cb\u30f3\u30b0\u306b\u3088\u308a\u30014\u500b\u306e\u5019\u88dc\u5316\u5408\u7269Mulberrin\u3001Quinine\u3001Quinidine\u3001Gartanin\u304c\u9078\u51fa\u3055\u308c\u307e\u3057\u305f\uff08Fig. Extra 2<\/strong>\uff09\u3002in vitro<\/em>\u30a2\u30c3\u30bb\u30a4\u306e\u7d50\u679c\u3001\u305d\u308c\u305e\u308c\u306eEC50\u5024\u306f2.1 \u00b5M\u30011.14 \u00b5M\u30011.71 \u00b5M\u30011.79 \u00b5M\u3067\u3042\u308a\u3001\u3044\u305a\u308c\u3082\u30b5\u30fc\u30c1\u30e5\u30a4\u30f3\u6d3b\u6027\u5316\u5408\u7269\u3068\u3057\u3066\u9069\u3057\u3066\u3044\u308b\u3053\u3068\u304c\u793a\u3055\u308c\u3066\u3044\u307e\u3059\u3002\u307e\u305f\u3001\u30c9\u30c3\u30ad\u30f3\u30b0\u89e3\u6790\u306b\u3088\u308a\u758e\u6c34\u6027\u76f8\u4e92\u4f5c\u7528\u306b\u91cd\u8981\u3068\u307f\u3089\u308c\u308bIle223\u3068Ile227\u304c\u63d0\u793a\u3055\u308c\u3001MM\/PB(SB)SA\u8a08\u7b97\u306b\u3088\u308a\u4e88\u6e2c\u3055\u308c\u305f\u7d50\u5408\u81ea\u7531\u30a8\u30cd\u30eb\u30ae\u30fc\u306fin vitro<\/em>\u30a2\u30c3\u30bb\u30a4\u306e\u7d50\u679c\u3068\u826f\u3044\u76f8\u95a2\u3092\u793a\u3057\u3066\u3044\u307e\u3059\u3002<\/p>\n\n\n\n

\"\"<\/figure>\n\n\n\n

Fig. Extra 2.<\/strong> \u898b\u51fa\u3055\u308c\u305f\u30b5\u30fc\u30c1\u30e5\u30a4\u30f3\u6d3b\u6027\u5316\u5408\u7269<\/p>\n\n\n\n


<\/p>\n","protected":false},"excerpt":{"rendered":"

\u3000\u5b66\u751f\u30a2\u30eb\u30d0\u30a4\u30c8K\u3055\u3093\u306eLigandScout\u95a2\u9023\u8ad6\u6587\u306e\u7d39\u4ecb\u8a18\u4e8b\u3067\u3059\uff0eLigandScout\u306e\u6d3b\u7528\u4e8b\u4f8b\u3068\u3057\u3066\u3054\u53c2\u8003\u306b\u306a\u308c\u3070\u5e78\u3044\u3067\u3059\uff0e \uff08\u4ee5\u4e0b\uff0c\u8ad6\u6587\u7d39\u4ecb\u8a18\u4e8b\uff09 \u672c\u8a18\u4e8b\u3067\u306f\u3001\u6b21\u306e\u8ad6\u6587\u3092\u3001LigandScout\u306e\u5229\u7528\u3092\u4e2d\u5fc3\u306b\u7d39…<\/p>\n","protected":false},"author":4,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[10],"tags":[73,60,72],"class_list":["post-968","post","type-post","status-publish","format-standard","hentry","category-ligandscout","tag-directory-of-useful-decoys","tag-pharmacophore","tag-sirt1"],"yoast_head":"\n\u8ad6\u6587\u7d39\u4ecb\uff08SIRT1\u6d3b\u6027\u5316\u5408\u7269\u306e\u63a2\u7d22\uff09 - In Silico \u5275\u85ac<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/\" \/>\n<meta property=\"og:locale\" content=\"ja_JP\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"\u8ad6\u6587\u7d39\u4ecb\uff08SIRT1\u6d3b\u6027\u5316\u5408\u7269\u306e\u63a2\u7d22\uff09 - In Silico \u5275\u85ac\" \/>\n<meta property=\"og:description\" content=\"\u3000\u5b66\u751f\u30a2\u30eb\u30d0\u30a4\u30c8K\u3055\u3093\u306eLigandScout\u95a2\u9023\u8ad6\u6587\u306e\u7d39\u4ecb\u8a18\u4e8b\u3067\u3059\uff0eLigandScout\u306e\u6d3b\u7528\u4e8b\u4f8b\u3068\u3057\u3066\u3054\u53c2\u8003\u306b\u306a\u308c\u3070\u5e78\u3044\u3067\u3059\uff0e \uff08\u4ee5\u4e0b\uff0c\u8ad6\u6587\u7d39\u4ecb\u8a18\u4e8b\uff09 \u672c\u8a18\u4e8b\u3067\u306f\u3001\u6b21\u306e\u8ad6\u6587\u3092\u3001LigandScout\u306e\u5229\u7528\u3092\u4e2d\u5fc3\u306b\u7d39...\" \/>\n<meta property=\"og:url\" content=\"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/\" \/>\n<meta property=\"og:site_name\" content=\"In Silico \u5275\u85ac\" \/>\n<meta property=\"article:published_time\" content=\"2020-02-07T04:15:35+00:00\" \/>\n<meta property=\"article:modified_time\" content=\"2022-02-22T05:50:18+00:00\" \/>\n<meta property=\"og:image\" content=\"https:\/\/www.insilico.jp\/blog\/wp-content\/uploads\/2020\/02\/1-s2.0-S1476927118306133-ga1_lrg-1024x699.jpg\" \/>\n<meta name=\"author\" content=\"\u7530\u5742\u53cb\u5f66\" \/>\n<meta name=\"twitter:card\" content=\"summary_large_image\" \/>\n<meta name=\"twitter:label1\" content=\"\u57f7\u7b46\u8005\" \/>\n\t<meta name=\"twitter:data1\" content=\"\u7530\u5742\u53cb\u5f66\" \/>\n\t<meta name=\"twitter:label2\" content=\"\u63a8\u5b9a\u8aad\u307f\u53d6\u308a\u6642\u9593\" \/>\n\t<meta name=\"twitter:data2\" content=\"12\u5206\" \/>\n<script type=\"application\/ld+json\" class=\"yoast-schema-graph\">{\"@context\":\"https:\/\/schema.org\",\"@graph\":[{\"@type\":\"WebPage\",\"@id\":\"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/\",\"url\":\"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/\",\"name\":\"\u8ad6\u6587\u7d39\u4ecb\uff08SIRT1\u6d3b\u6027\u5316\u5408\u7269\u306e\u63a2\u7d22\uff09 - In Silico \u5275\u85ac\",\"isPartOf\":{\"@id\":\"https:\/\/www.insilico.jp\/blog\/#website\"},\"primaryImageOfPage\":{\"@id\":\"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/#primaryimage\"},\"image\":{\"@id\":\"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/#primaryimage\"},\"thumbnailUrl\":\"https:\/\/www.insilico.jp\/blog\/wp-content\/uploads\/2020\/02\/1-s2.0-S1476927118306133-ga1_lrg-1024x699.jpg\",\"datePublished\":\"2020-02-07T04:15:35+00:00\",\"dateModified\":\"2022-02-22T05:50:18+00:00\",\"author\":{\"@id\":\"https:\/\/www.insilico.jp\/blog\/#\/schema\/person\/562753b8fea016d8ef340763aa41deeb\"},\"breadcrumb\":{\"@id\":\"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/#breadcrumb\"},\"inLanguage\":\"ja\",\"potentialAction\":[{\"@type\":\"ReadAction\",\"target\":[\"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/\"]}]},{\"@type\":\"ImageObject\",\"inLanguage\":\"ja\",\"@id\":\"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/#primaryimage\",\"url\":\"https:\/\/www.insilico.jp\/blog\/wp-content\/uploads\/2020\/02\/1-s2.0-S1476927118306133-ga1_lrg.jpg\",\"contentUrl\":\"https:\/\/www.insilico.jp\/blog\/wp-content\/uploads\/2020\/02\/1-s2.0-S1476927118306133-ga1_lrg.jpg\",\"width\":1298,\"height\":886},{\"@type\":\"BreadcrumbList\",\"@id\":\"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/#breadcrumb\",\"itemListElement\":[{\"@type\":\"ListItem\",\"position\":1,\"name\":\"\u30db\u30fc\u30e0\",\"item\":\"https:\/\/www.insilico.jp\/blog\/\"},{\"@type\":\"ListItem\",\"position\":2,\"name\":\"\u8ad6\u6587\u7d39\u4ecb\uff08SIRT1\u6d3b\u6027\u5316\u5408\u7269\u306e\u63a2\u7d22\uff09\"}]},{\"@type\":\"WebSite\",\"@id\":\"https:\/\/www.insilico.jp\/blog\/#website\",\"url\":\"https:\/\/www.insilico.jp\/blog\/\",\"name\":\"In Silico \u5275\u85ac\",\"description\":\"\u3053\u306e\u30d6\u30ed\u30b0\u30b5\u30a4\u30c8\u306f\u3001In silico\u5275\u85ac\u306b\u95a2\u9023\u3059\u308b\u7814\u7a76\u8ad6\u6587\u3084\u30bd\u30d5\u30c8\u30a6\u30a7\u30a2\u30fb\u30c4\u30fc\u30eb\u306e\u5229\u7528\u3084\u30d7\u30ed\u30b0\u30e9\u30df\u30f3\u30b0\u306a\u3069\u306b\u3064\u3044\u3066\u3054\u7d39\u4ecb\u3057\u3066\u3044\u307e\u3059\u3002\",\"potentialAction\":[{\"@type\":\"SearchAction\",\"target\":{\"@type\":\"EntryPoint\",\"urlTemplate\":\"https:\/\/www.insilico.jp\/blog\/?s={search_term_string}\"},\"query-input\":{\"@type\":\"PropertyValueSpecification\",\"valueRequired\":true,\"valueName\":\"search_term_string\"}}],\"inLanguage\":\"ja\"},{\"@type\":\"Person\",\"@id\":\"https:\/\/www.insilico.jp\/blog\/#\/schema\/person\/562753b8fea016d8ef340763aa41deeb\",\"name\":\"\u7530\u5742\u53cb\u5f66\",\"image\":{\"@type\":\"ImageObject\",\"inLanguage\":\"ja\",\"@id\":\"https:\/\/www.insilico.jp\/blog\/#\/schema\/person\/image\/\",\"url\":\"https:\/\/secure.gravatar.com\/avatar\/3fc25edbb30cf9aa4c787fcbbfa2fa4d?s=96&d=mm&r=g\",\"contentUrl\":\"https:\/\/secure.gravatar.com\/avatar\/3fc25edbb30cf9aa4c787fcbbfa2fa4d?s=96&d=mm&r=g\",\"caption\":\"\u7530\u5742\u53cb\u5f66\"},\"description\":\"President of Affinity Science Corporation\",\"url\":\"https:\/\/www.insilico.jp\/blog\/author\/tasaka\/\"}]}<\/script>\n<!-- \/ Yoast SEO plugin. -->","yoast_head_json":{"title":"\u8ad6\u6587\u7d39\u4ecb\uff08SIRT1\u6d3b\u6027\u5316\u5408\u7269\u306e\u63a2\u7d22\uff09 - In Silico \u5275\u85ac","robots":{"index":"index","follow":"follow","max-snippet":"max-snippet:-1","max-image-preview":"max-image-preview:large","max-video-preview":"max-video-preview:-1"},"canonical":"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/","og_locale":"ja_JP","og_type":"article","og_title":"\u8ad6\u6587\u7d39\u4ecb\uff08SIRT1\u6d3b\u6027\u5316\u5408\u7269\u306e\u63a2\u7d22\uff09 - In Silico \u5275\u85ac","og_description":"\u3000\u5b66\u751f\u30a2\u30eb\u30d0\u30a4\u30c8K\u3055\u3093\u306eLigandScout\u95a2\u9023\u8ad6\u6587\u306e\u7d39\u4ecb\u8a18\u4e8b\u3067\u3059\uff0eLigandScout\u306e\u6d3b\u7528\u4e8b\u4f8b\u3068\u3057\u3066\u3054\u53c2\u8003\u306b\u306a\u308c\u3070\u5e78\u3044\u3067\u3059\uff0e \uff08\u4ee5\u4e0b\uff0c\u8ad6\u6587\u7d39\u4ecb\u8a18\u4e8b\uff09 \u672c\u8a18\u4e8b\u3067\u306f\u3001\u6b21\u306e\u8ad6\u6587\u3092\u3001LigandScout\u306e\u5229\u7528\u3092\u4e2d\u5fc3\u306b\u7d39...","og_url":"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/","og_site_name":"In Silico \u5275\u85ac","article_published_time":"2020-02-07T04:15:35+00:00","article_modified_time":"2022-02-22T05:50:18+00:00","og_image":[{"url":"https:\/\/www.insilico.jp\/blog\/wp-content\/uploads\/2020\/02\/1-s2.0-S1476927118306133-ga1_lrg-1024x699.jpg","type":"","width":"","height":""}],"author":"\u7530\u5742\u53cb\u5f66","twitter_card":"summary_large_image","twitter_misc":{"\u57f7\u7b46\u8005":"\u7530\u5742\u53cb\u5f66","\u63a8\u5b9a\u8aad\u307f\u53d6\u308a\u6642\u9593":"12\u5206"},"schema":{"@context":"https:\/\/schema.org","@graph":[{"@type":"WebPage","@id":"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/","url":"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/","name":"\u8ad6\u6587\u7d39\u4ecb\uff08SIRT1\u6d3b\u6027\u5316\u5408\u7269\u306e\u63a2\u7d22\uff09 - In Silico \u5275\u85ac","isPartOf":{"@id":"https:\/\/www.insilico.jp\/blog\/#website"},"primaryImageOfPage":{"@id":"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/#primaryimage"},"image":{"@id":"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/#primaryimage"},"thumbnailUrl":"https:\/\/www.insilico.jp\/blog\/wp-content\/uploads\/2020\/02\/1-s2.0-S1476927118306133-ga1_lrg-1024x699.jpg","datePublished":"2020-02-07T04:15:35+00:00","dateModified":"2022-02-22T05:50:18+00:00","author":{"@id":"https:\/\/www.insilico.jp\/blog\/#\/schema\/person\/562753b8fea016d8ef340763aa41deeb"},"breadcrumb":{"@id":"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/#breadcrumb"},"inLanguage":"ja","potentialAction":[{"@type":"ReadAction","target":["https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/"]}]},{"@type":"ImageObject","inLanguage":"ja","@id":"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/#primaryimage","url":"https:\/\/www.insilico.jp\/blog\/wp-content\/uploads\/2020\/02\/1-s2.0-S1476927118306133-ga1_lrg.jpg","contentUrl":"https:\/\/www.insilico.jp\/blog\/wp-content\/uploads\/2020\/02\/1-s2.0-S1476927118306133-ga1_lrg.jpg","width":1298,"height":886},{"@type":"BreadcrumbList","@id":"https:\/\/www.insilico.jp\/blog\/2020\/02\/07\/sirt1_ligand\/#breadcrumb","itemListElement":[{"@type":"ListItem","position":1,"name":"\u30db\u30fc\u30e0","item":"https:\/\/www.insilico.jp\/blog\/"},{"@type":"ListItem","position":2,"name":"\u8ad6\u6587\u7d39\u4ecb\uff08SIRT1\u6d3b\u6027\u5316\u5408\u7269\u306e\u63a2\u7d22\uff09"}]},{"@type":"WebSite","@id":"https:\/\/www.insilico.jp\/blog\/#website","url":"https:\/\/www.insilico.jp\/blog\/","name":"In Silico \u5275\u85ac","description":"\u3053\u306e\u30d6\u30ed\u30b0\u30b5\u30a4\u30c8\u306f\u3001In silico\u5275\u85ac\u306b\u95a2\u9023\u3059\u308b\u7814\u7a76\u8ad6\u6587\u3084\u30bd\u30d5\u30c8\u30a6\u30a7\u30a2\u30fb\u30c4\u30fc\u30eb\u306e\u5229\u7528\u3084\u30d7\u30ed\u30b0\u30e9\u30df\u30f3\u30b0\u306a\u3069\u306b\u3064\u3044\u3066\u3054\u7d39\u4ecb\u3057\u3066\u3044\u307e\u3059\u3002","potentialAction":[{"@type":"SearchAction","target":{"@type":"EntryPoint","urlTemplate":"https:\/\/www.insilico.jp\/blog\/?s={search_term_string}"},"query-input":{"@type":"PropertyValueSpecification","valueRequired":true,"valueName":"search_term_string"}}],"inLanguage":"ja"},{"@type":"Person","@id":"https:\/\/www.insilico.jp\/blog\/#\/schema\/person\/562753b8fea016d8ef340763aa41deeb","name":"\u7530\u5742\u53cb\u5f66","image":{"@type":"ImageObject","inLanguage":"ja","@id":"https:\/\/www.insilico.jp\/blog\/#\/schema\/person\/image\/","url":"https:\/\/secure.gravatar.com\/avatar\/3fc25edbb30cf9aa4c787fcbbfa2fa4d?s=96&d=mm&r=g","contentUrl":"https:\/\/secure.gravatar.com\/avatar\/3fc25edbb30cf9aa4c787fcbbfa2fa4d?s=96&d=mm&r=g","caption":"\u7530\u5742\u53cb\u5f66"},"description":"President of Affinity Science Corporation","url":"https:\/\/www.insilico.jp\/blog\/author\/tasaka\/"}]}},"_links":{"self":[{"href":"https:\/\/www.insilico.jp\/blog\/wp-json\/wp\/v2\/posts\/968","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.insilico.jp\/blog\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.insilico.jp\/blog\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.insilico.jp\/blog\/wp-json\/wp\/v2\/users\/4"}],"replies":[{"embeddable":true,"href":"https:\/\/www.insilico.jp\/blog\/wp-json\/wp\/v2\/comments?post=968"}],"version-history":[{"count":2,"href":"https:\/\/www.insilico.jp\/blog\/wp-json\/wp\/v2\/posts\/968\/revisions"}],"predecessor-version":[{"id":1967,"href":"https:\/\/www.insilico.jp\/blog\/wp-json\/wp\/v2\/posts\/968\/revisions\/1967"}],"wp:attachment":[{"href":"https:\/\/www.insilico.jp\/blog\/wp-json\/wp\/v2\/media?parent=968"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.insilico.jp\/blog\/wp-json\/wp\/v2\/categories?post=968"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.insilico.jp\/blog\/wp-json\/wp\/v2\/tags?post=968"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}