Lambda-dynamics free energy simulation methods.
Lambda-dynamics free energy simulation methods.
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DOI：
10.1002/jcc.21295
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发表时间：
2009-08
影响因子：
3
通讯作者：
Brooks, Charles L., III
中科院分区：
文献类型：
--
作者：
Knight, Jennifer L.;Brooks, Charles L., III
自由能计算是获得许多重要生物现象的精确理论估计的基础，这些生物现象包括水化能、蛋白质-配体结合亲和力和构象变化的能量学。与传统的自由能摄动和热力学积分方法不同，λ-Dynamic将传统的“λ”视为自由能模拟中的动态变量，并在一次模拟中同时评估多个状态的热力学性质。在本文中，我们提供了λ动力学理论的概述，包括使用偏置和抑制势来促进构象采样。我们回顾了λ动力学如何被用于快速可靠地计算一系列配体的相对水化自由能和结合亲和力，准确地识别从错误取向开始的结晶学观察到的结合模式，以及模拟突变对蛋白质稳定性的影响。最后，我们建议如何扩展λ-Dynamic以促进基于结构的药物设计中的建模工作。
Free energy calculations are fundamental to obtaining accurate theoretical estimates of many important biological phenomena including hydration energies, protein-ligand binding affinities and energetics of conformational changes. Unlike traditional free energy perturbation and thermodynamic integration methods, λ-dynamics treats the conventional "λ" as a dynamic variable in free energy simulations and simultaneously evaluates thermodynamic properties for multiple states in a single simulation. In the present paper, we provide an overview of the theory of λ-dynamics, including the use of biasing and restraining potentials to facilitate conformational sampling. We review how λ-dynamics has been used to rapidly and reliably compute relative hydration free energies and binding affinities for series of ligands, to accurately identify crystallographically observed binding modes starting from incorrect orientations, and to model the effects of mutations upon protein stability. Finally, we suggest how λ-dynamics may be extended to facilitate modeling efforts in structure-based drug design.
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影响因子：
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作者：
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通讯作者：
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影响因子：
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