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作为药物靶点的RNA:化学、建模及进化工具

RNA as a drug target: chemical, modelling, and evolutionary tools.

作者信息

Hermann T, Westhof E

机构信息

Institut de Biologie Moléculaire et Cellulaire du CNRS, Strasbourg, France.

出版信息

Curr Opin Biotechnol. 1998 Feb;9(1):66-73. doi: 10.1016/s0958-1669(98)80086-4.

Abstract

Dramatic technical progress in RNA synthesis and structure determination has allowed several difficulties inherent to the preparation, handling and structural analysis of RNA to be overcome, and this has led to a wealth of information about RNA structure and its relationship with biological function. It is now fully recognized that RNA molecules intervene at all stages of cell life, not only because of key sequence motifs but also because of intricate three-dimensional folds. This realization has promoted RNA to a potential therapeutic target. As in protein motifs recognizing nucleic acids, groups of the molecule interacting with RNA contribute to specific binding through defined hydrogen bonds and van der Waals docking, while other parts contribute to the driving force of binding via less specific electrostatic interactions accompanied by water and ion displacement.

摘要

RNA合成与结构测定方面取得的巨大技术进步,使得RNA制备、处理及结构分析过程中固有的一些难题得以克服,这也带来了大量有关RNA结构及其与生物学功能关系的信息。现在人们已充分认识到,RNA分子在细胞生命的各个阶段都发挥着作用,这不仅是因为关键序列基序,还因为其复杂的三维折叠结构。这一认识促使RNA成为一个潜在的治疗靶点。如同蛋白质基序识别核酸一样,与RNA相互作用的分子基团通过特定的氢键和范德华对接作用实现特异性结合,而其他部分则通过不太特异的静电相互作用以及水和离子的位移来提供结合的驱动力。

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