Ziada Sonia, Braka Abdennour, Diharce Julien, Aci-Sèche Samia, Bonnet Pascal
Institut de Chimie Organique et Analytique (ICOA), UMR7311 CNRS-Université d'Orléans , Université d'Orléans, Orléans Cedex 2, France.
Centre de Biophysique Moléculaire (CBM), CNRS, UPR 4301, Orléans Cedex 2, France.
Methods Mol Biol. 2018;1762:403-426. doi: 10.1007/978-1-4939-7756-7_20.
Nobel Laureate Richard P. Feynman stated: "[…] everything that living things do can be understood in terms of jiggling and wiggling of atoms […]." The importance of computer simulations of macromolecules, which use classical mechanics principles to describe atom behavior, is widely acknowledged and nowadays, they are applied in many fields such as material sciences and drug discovery. With the increase of computing power, molecular dynamics simulations can be applied to understand biological mechanisms at realistic timescales. In this chapter, we share our computational experience providing a global view of two of the widely used enhanced molecular dynamics methods to study protein structure and dynamics through the description of their characteristics, limits and we provide some examples of their applications in drug design. We also discuss the appropriate choice of software and hardware. In a detailed practical procedure, we describe how to set up, run, and analyze two main molecular dynamics methods, the umbrella sampling (US) and the accelerated molecular dynamics (aMD) methods.
诺贝尔奖获得者理查德·P·费曼曾说过：“[…] 生物所做的一切都可以用原子的振动和摆动来理解 […]。” 利用经典力学原理描述原子行为的大分子计算机模拟的重要性已得到广泛认可，如今，它们被应用于许多领域，如材料科学和药物发现。随着计算能力的提高，分子动力学模拟可用于在实际时间尺度上理解生物机制。在本章中，我们分享我们的计算经验，通过描述两种广泛使用的增强分子动力学方法的特点、局限性，提供对它们的全局视图，以研究蛋白质结构和动力学，并提供它们在药物设计中的一些应用实例。我们还讨论了软件和硬件的适当选择。在一个详细的实际操作过程中，我们描述了如何设置、运行和分析两种主要的分子动力学方法，即伞形采样（US）和加速分子动力学（aMD）方法。
