Bitencourt-Ferreira Gabriela, de Azevedo Walter Filgueira
Escola de Ciências da Saúde, Pontifícia Universidade Católica do Rio Grande do Sul-PUCRS, Porto Alegre, RS, Brazil.
Methods Mol Biol. 2019;2053:35-50. doi: 10.1007/978-1-4939-9752-7_3.
Protein-ligand docking simulations are of central interest for computer-aided drug design. Docking is also of pivotal importance to understand the structural basis for protein-ligand binding affinity. In the last decades, we have seen an explosion in the number of three-dimensional structures of protein-ligand complexes available at the Protein Data Bank. These structures gave further support for the development and validation of in silico approaches to address the binding of small molecules to proteins. As a result, we have now dozens of open source programs and web servers to carry out molecular docking simulations. The development of the docking programs and the success of such simulations called the attention of a broad spectrum of researchers not necessarily familiar with computer simulations. In this scenario, it is essential for those involved in experimental studies of protein-ligand interactions and biophysical techniques to have a glimpse of the basics of the protein-ligand docking simulations. Applications of protein-ligand docking simulations to drug development and discovery were able to identify hits, inhibitors, and even drugs. In the present chapter, we cover the fundamental ideas behind protein-ligand docking programs for non-specialists, which may benefit from such knowledge when studying molecular recognition mechanism.
蛋白质-配体对接模拟是计算机辅助药物设计的核心研究内容。对接对于理解蛋白质-配体结合亲和力的结构基础也至关重要。在过去几十年里，我们看到蛋白质数据银行中可获取的蛋白质-配体复合物三维结构数量呈爆炸式增长。这些结构为开发和验证用于研究小分子与蛋白质结合的计算机模拟方法提供了进一步支持。因此，我们现在有几十种开源程序和网络服务器来进行分子对接模拟。对接程序的发展以及此类模拟的成功引起了广泛研究人员的关注，他们不一定熟悉计算机模拟。在这种情况下，对于参与蛋白质-配体相互作用实验研究和生物物理技术的人员来说，了解蛋白质-配体对接模拟的基础知识至关重要。蛋白质-配体对接模拟在药物开发和发现中的应用能够识别出命中物、抑制剂甚至药物。在本章中，我们为非专业人士介绍蛋白质-配体对接程序背后的基本概念，他们在研究分子识别机制时可能会受益于这些知识。
