{"id":3857,"date":"2016-11-02T10:01:54","date_gmt":"2016-11-02T02:01:54","guid":{"rendered":"http:\/\/www.moldesigner.com\/?p=86"},"modified":"2022-03-24T15:52:10","modified_gmt":"2022-03-24T07:52:10","slug":"would-you-trust-a-machine-to-perform-surgical-procedures","status":"publish","type":"post","link":"https:\/\/www.moldesigner.com\/?p=3857","title":{"rendered":"GPCR \u5bfc\u5411\u7597\u6cd5\u7684\u66ff\u4ee3\u65b9\u6848 | G \u86cb\u767d\u8c03\u8282\u5242"},"content":{"rendered":"

[\u5206\u8fea\u89c2\u70b9]\uff1a\u901a\u8fc7\u80bd\u5e93\u7b5b\u9009\u548c\u836f\u7269\u5316\u5b66\u7684\u7ed3\u5408\uff0c\u6ce2\u6069\u5927\u5b66\u7684\u7814\u7a76\u4eba\u5458\u6210\u529f\u53d1\u73b0\u4e86\u4e00\u7c7b\u65b0\u7684\u5177\u6709\u7ec6\u80de\u6e17\u900f\u6027\u548cG\u03b1i\/s \u9009\u62e9\u6027\u7684\u80bd\u57fa\u8c03\u8282\u5242\uff0c\u80fd\u591f\u53ef\u9006\u5730\u8c03\u8282G\u03b1 \u86cb\u767d\u6d3b\u6027\uff0c\u4e3a G\u03b1i\/s \u76f4\u63a5\u8c03\u8282\u5242\u7684\u5f00\u53d1\u8bc1\u660e\u4e86\u53ef\u884c\u6027\u3002<\/strong><\/p>\n<\/div>

<\/span><\/div>
FDA \u6279\u51c6\u7684\u836f\u7269\u4e2d\u5927\u7ea6\u6709 30%\u00a0\u9776\u5411 GPCR\u3002\u7136\u800c\uff0c\u9776\u5411 GPCR \u5177\u6709\u56fa\u6709\u7684\u5c40\u9650\u6027\u3002\u67d0\u4e9b\u75be\u75c5\u53ef\u80fd\u6d89\u53ca\u591a\u4e2a GPCR\uff0c\u800c\u6bcf\u4e2a GPCR \u90fd\u4ecb\u5bfc\u7279\u5b9a\u7684 G \u86cb\u767d\u4fe1\u53f7\u4f20\u5bfc\u3002\u540c\u65f6\uff0c\u7279\u5b9a\u60c5\u51b5\u4e0b\uff0cG \u86cb\u767d\u4e5f\u53ef\u80fd\u542f\u52a8\u72ec\u7acb\u4e8e GPCR \u7684\u4fe1\u53f7\u901a\u8def\u3002<\/section>\n
\u56e0\u6b64\uff0c\u76f4\u63a5\u9776\u5411\u7ec6\u80de\u5185 G \u86cb\u767d\u4ee3\u8868\u4e86 GPCR \u5bfc\u5411\u7597\u6cd5\u7684\u4e00\u79cd\u66ff\u4ee3\u65b9\u6848\u3002<\/strong>\u4f46\u662f\uff0cG \u86cb\u767d\u8868\u9762\u4e0a\u6ca1\u6709\u660e\u786e\u5b9a\u4e49\u7684\u7ed3\u5408\u90e8\u4f4d\uff0c\u96be\u4ee5\u7528\u5e38\u89c4\u5c0f\u5206\u5b50\u9776\u5411\u3002\u800c\u4e14\uff0cG \u86cb\u767d\u7684\u4e0d\u540c\u4e9a\u65cf\u5177\u6709\u9ad8\u5ea6\u7684\u5e8f\u5217\u548c\u7ed3\u6784\u76f8\u4f3c\u6027\uff0c\u5f88\u96be\u5b9e\u73b0\u7279\u5f02\u6027\u7684\u9776\u5411\u3002<\/section>\n

\u8fc4\u4eca\u4e3a\u6b62\uff0c\u53ea\u6709 FR900359 (FR) \u548c YM-254890 (YM)\u7b49\u5c11\u6570\u7279\u5b9a\u7684 G \u86cb\u767d\u8c03\u8282\u5242\u662f\u5df2\u77e5\u7684\uff0c\u800c\u4e14\u5b83\u4eec\u5747\u4e3a\u9776\u5411 G\u03b1q \u7684\u5929\u7136\u73af\u72b6\u80bd\u3002\u53d7\u6b64\u542f\u53d1\uff0c\u7814\u7a76\u4eba\u5458\u7b5b\u9009\u4e86\u4e00\u682a\u4e00\u7269\u5316\u5b66\u7ec4\u5408\u591a\u80bd\u5e93\u00a0(OBOC)\u00a0\uff0c\u4ece\u4e2d\u53d1\u73b0\u4e86\u4e00\u79cd\u76f8\u5bf9\u6709\u6548\u7684 G\u03b1i1\u00b7GDP \u8c03\u8282\u5242 GPM-1\u3002<\/p>\n<\/div>

<\/span><\/div>

\u968f\u540e\u5bf9 GPM-1 \u8fdb\u884c\u4f18\u5316\u63d0\u9ad8\u5176\u7ed3\u5408\u4eb2\u548c\u529b\u548c\u86cb\u767d\u6c34\u89e3\u7a33\u5b9a\u6027\uff0c\u5e76\u4e0e\u7ec6\u80de\u7a7f\u900f\u80bd (CPP) \u7ed3\u5408\u63d0\u9ad8\u5176\u7ec6\u80de\u6e17\u900f\u6027\u3002\u7814\u7a76\u7ed3\u679c\u8868\u660e\uff0cGPM-1 \u7684\u53d8\u4f53GPM 1c \u548c GPM-1d \u53ef\u4ee5\u901a\u8fc7\u7c7b\u4f3c\u9e1f\u560c\u5464-\u6838\u82f7\u9178\u4ea4\u6362\u8c03\u8282\u5242\uff08GEM\uff09 \u7684\u65b9\u5f0f\u8c03\u8282\u7ec6\u80de\u57f9\u517b\u4e2d\u7684 G\u03b1i\/s \u6d3b\u6027\uff0c\u5373\u4f5c\u4e3a G\u03b1i \u7684\u9e1f\u560c\u5464\u6838\u82f7\u9178\u4ea4\u6362\u56e0\u5b50 (GEF) \u548c G\u03b1s \u7684\u9e1f\u560c\u5464\u6838\u82f7\u9178\u89e3\u79bb\u6291\u5236\u5242 (GDI)\uff0c\u5177\u6709\u53cc\u529f\u80fd\u6d3b\u6027\u3002<\/p>\n<\/div>

<\/span><\/div>

\u4e3a\u4e86\u6df1\u5165\u4e86\u89e3\u591a\u80bd\u7684\u751f\u7269\u6d3b\u6027\u7ed3\u6784\u57fa\u7840\uff0c\u7814\u7a76\u4eba\u5458\u5bf9 G\u03b1i\/s \u4e0e\u5b9e\u9a8c\u4e0a\u88ab\u8ba4\u4e3a\u5177\u6709\u6d3b\u6027\u7684\u80bd\u8c03\u8282\u5242\uff08GPM-1c\u3001GPM-1d\uff09\u7684\u76f8\u4e92\u4f5c\u7528\u8fdb\u884c\u4e86\u4e00\u7cfb\u5217\u8ba1\u7b97\u5206\u6790\u3002\u9996\u5148\uff0c\u901a\u8fc7\u00a0YASARA\u00a0\u751f\u6210G\u03b1i1\u4ee5\u53caGPM-1 \u548cGPM-1b-d\u7b49\u80bd\u76843D\u7ed3\u6784\uff0c\u540e\u901a\u8fc7\u00a0SeeSAR\u00a0\u4e2d\u7684\u00a0DoGSiteScorer\u00a0\u7b97\u6cd5\u9884\u6d4b\u80bd\u53ef\u80fd\u6027\u7684\u7ed3\u5408\u4f4d\u70b9\uff0c\u5e76\u901a\u8fc7 YASARA \u4e2d\u7684VINA\u7b97\u6cd5\u8fdb\u884c\u5bf9\u63a5\u3002<\/p>\n<\/div>

<\/span><\/div>
DoGSiteScorer\u00a0\u9884\u6d4b\u7684\u7ed3\u5408\u53e3\u888b<\/strong><\/h6>\n<\/div>

\u968f\u540e\u5bf9 GPM-1c \u4e0e G\u03b1i\/s \u7ed3\u5408\u540e GDP \u7684\u7ed3\u5408\u4eb2\u548c\u529b\u53d8\u5316\u8fdb\u884c\u89c6\u89c9\u8bc4\u4f30\uff0c\u5176\u4e2d\u539f\u5b50\u5bf9\u7ed3\u5408\u4eb2\u548c\u529b\u7684\u8d21\u732e\u7531\u00a0SeeSAR \u4e2d\u7684 HYDE \u8bc4\u5206\u51fd\u6570\u8ba1\u7b97\u3002\u7eff\u8272\u7403\u4f53\u8868\u793a\u5bf9\u7ed3\u5408\u4eb2\u548c\u529b\u6709\u79ef\u6781\u7684\u8d21\u732e\uff0c\u7ea2\u8272\u7403\u4f53\u8868\u793a\u5bf9\u7ed3\u5408\u4eb2\u548c\u529b\u6709\u4e0d\u5229\u7684\u8d21\u732e\uff0c\u7403\u4f53\u7684\u5927\u5c0f\u548c\u5f71\u54cd\u6210\u6b63\u6bd4\u3002<\/p>\n<\/div>

<\/span><\/div>
HYDE\u00a0\u8bc4\u4f30\u7ed3\u5408\u4eb2\u548c\u529b<\/strong><\/h6>\n<\/div>

\u5728 a \u548c b \u4e2d\uff0c\u9876\u90e8\u7ed3\u6784\u8868\u793a\u521d\u59cb\u7ed3\u6784\uff0c\u4e0b\u90e8\u8868\u793aMD\u00a050ns \u540e\u7684\u7ed3\u6784\u3002\u4ece\u56fe\u4e2d\u53ef\u4ee5\u770b\u51fa\uff0cGPM-1c \u548c G\u03b1i \u7ed3\u5408\u540e\uff0c\u7ea2\u8272\u7684\u7403\u4f53\u6574\u4f53\u589e\u52a0\uff08\u5de6\u4fa7\u7070\u8272\uff09\uff0c\u8868\u660e GDP \u548c G\u03b1i \u4e4b\u95f4\u4e0d\u5229\u7684\u76f8\u4e92\u4f5c\u7528\u589e\u52a0\uff0c\u5373\u80bd\u7684\u7ed3\u5408\u53ef\u80fd\u4fc3\u8fdb G\u03b1i \u91ca\u653e GDP\uff0c\u5177\u6709\u7c7b\u4f3c GEF \u7684\u4f5c\u7528<\/strong>\u3002GPM-1c \u548c G\u03b1s \u7ed3\u5408\u524d\u540e\u7684\u60c5\u51b5\u5219\u76f8\u53cd\uff0c\u7ea2\u8272\u7684\u7403\u4f53\u6574\u4f53\u51cf\u5c11\uff08\u53f3\u4fa7\u6a58\u7ea2\u8272\uff09\uff0c\u8868\u660e GDP \u548c G\u03b1s \u4e4b\u95f4\u4e0d\u5229\u7684\u76f8\u4e92\u4f5c\u7528\u964d\u4f4e\uff0c\u5373\u00a0GPM-1c\u00a0\u6539\u5584\u4e86 GDP \u4e0e G\u03b1s \u7684\u7ed3\u5408\uff0c\u5177\u6709\u7c7b\u4f3c GDI \u7684\u4f5c\u7528\u3002<\/strong><\/p>\n

\u5728\u8fd9\u9879\u5de5\u4f5c\u4e2d\uff0c\u7814\u7a76\u4eba\u5458\u901a\u8fc7\u80bd\u5e93\u7b5b\u9009\u548c\u836f\u7269\u5316\u5b66\u7684\u7ed3\u5408\u53d1\u73b0\u4e86\u7ebf\u6027 (GPM-1c) \u548c\u73af\u80bd (GPM-1d) \u53ef\u4f5c\u4e3a\u4e00\u7c7b\u65b0\u7684\u7ec6\u80de\u6e17\u900f\u6027\u3001G\u03b1i\/s \u9009\u62e9\u6027\u548c G\u03b1 \u86cb\u767d\u6d3b\u6027\u53ef\u9006\u8c03\u8282\u5242\uff0c\u4e3a\u540e\u7eed\u836f\u7406\u5b66\u7684\u7814\u7a76\u4ee5\u53ca\u57fa\u4e8eGs \u548c Gi\u5f00\u53d1\u6cbb\u7597\u5242\u5960\u5b9a\u4e86\u57fa\u7840\u3002<\/strong><\/section>\n<\/div>

\u00a0 \u53c2\u8003\u8d44\u6599\u00a0\u00a0<\/strong><\/p>\n

Targeting G\u03b1i\/s Proteins with Peptidyl Nucleotide Exchange Modulators<\/p>\n

https:\/\/pubs.acs.org\/doi\/10.1021\/acschembio.1c00929<\/p>\n<\/div><\/div><\/div><\/div><\/div>\n","protected":false},"excerpt":{"rendered":"

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