Department of Pharmacy and Biotechnology, Alma Mater Studiorum-Università di Bologna, Bologna, Italy.
Scuola Internazionale Superiore di Studi Avanzati, Trieste, Italy.
Methods Mol Biol. 2020;2141:391-411. doi: 10.1007/978-1-0716-0524-0_19.
Molecular dynamics simulations represent a powerful tool to gain insights into structural and dynamical features of biomolecular systems. Nevertheless, their recognized limitation in terms of achievable timescales becomes particularly severe when dealing with slow processes. In such cases, the employment of enhanced sampling methods, which allow accelerating the characterization of rare events in a timeframe consistent with conventional computational resources, results as crucial. In particular, such advanced techniques have proven highly valuable in the context of protein folding and, specifically, to explore the conformational ensemble spanned by intrinsically disordered proteins (IDPs). Here, we describe how to set up molecular dynamics simulations with one of these enhanced sampling approaches (namely, Parallel Tempering Metadynamics in the Well-Tempered Ensemble) using the N peptide as a test case.
分子动力学模拟是一种深入了解生物分子系统结构和动力学特征的有力工具。然而，当涉及到缓慢的过程时，其在可实现时间尺度方面的公认局限性变得尤为严重。在这种情况下，采用增强采样方法是至关重要的，这些方法可以在与传统计算资源一致的时间范围内加速稀有事件的特征描述。特别是，这些先进的技术在蛋白质折叠的背景下已经被证明非常有价值，特别是在探索固有无序蛋白质（IDP）所涵盖的构象集合方面。在这里，我们将描述如何使用 N 肽作为测试案例，使用其中一种增强采样方法（即 Well-Tempered Ensemble 中的并行温度介动力学）来设置分子动力学模拟。
