Weill Nathanael, Therrien Eric, Campagna-Slater Valérie, Moitessier Nicolas
Department of Chemistry, McGill University, 801 Sherbrooke St W, Montreal, QC, Canada H3A 0B8.
Curr Pharm Des. 2014;20(20):3338-59. doi: 10.2174/13816128113199990605.
Over the last two decades, computationally docking potential protein ligands (e.g., enzyme inhibitors) has become one of the most widely used strategies in computer aided drug design. While these docking methods were developed, some effort focused on their user-friendliness up to a point where they can be used by non-experts with nearly no training, somewhat hiding the underlying theory. However, basic knowledge is still required to avoid pitfalls and misinterpretations of docking experiments. Over the years, we have collected the common mistakes and necessary information for the proper use of docking programs. In this review, we compiled this data for non-experts in the field. In a first section, we present the theory of docking and scoring approaches as well as their limitations, followed by the most recent progress towards the consideration of protein flexibility, water molecules, metal ions, and covalent drugs. In a second section, we describe what we believe are the necessary steps to ensure optimal docking. More specifically, we present the selection of a docking program, available databases of small molecules, macromolecules and biological data, the necessary steps for the preparation of proteins and small molecules, and finally post docking analysis techniques. In the following sections, we compile the sources of biases and describe docking to nucleic acids.
在过去二十年中，通过计算对接潜在的蛋白质配体（如酶抑制剂）已成为计算机辅助药物设计中使用最广泛的策略之一。在开发这些对接方法时，人们在一定程度上致力于提高其用户友好性，使得几乎无需培训的非专业人员也能够使用，这在一定程度上掩盖了其背后的理论。然而，仍需要具备基础知识以避免对接实验中出现失误和误解。多年来，我们收集了对接程序正确使用过程中的常见错误和必要信息。在本综述中，我们为该领域的非专业人员整理了这些数据。在第一部分，我们介绍对接和评分方法的理论及其局限性，随后阐述在考虑蛋白质柔性、水分子、金属离子和共价药物方面的最新进展。在第二部分，我们描述了我们认为确保最佳对接所需的步骤。更具体地说，我们介绍对接程序的选择、小分子、大分子和生物数据的可用数据库、蛋白质和小分子制备的必要步骤，以及最后的对接后分析技术。在接下来的部分中，我们汇总偏差来源并描述与核酸的对接。
