Laboratoire de Biochimie Théorique, CNRS, UPR9080, Université Paris Diderot, Sorbonne Paris Cité, Institut de Biologie Physico-Chimique, Paris, France.
Phys Chem Chem Phys. 2012 Jan 14;14(2):877-86. doi: 10.1039/c1cp21779h. Epub 2011 Nov 25.
One challenge in computational biophysics and biology is to develop methodologies able to estimate accurately the configurational entropy of macromolecules. Among many methods, the quasiharmonic approximation (QH) is most widely used as it is simple in both theory and implementation. However, it has been shown that this method becomes inaccurate by overestimating entropy for systems with rugged free energy landscapes. Here, we propose a simple method to improve the QH approximation, i.e., to reduce QH entropy. We approximate the potential energy landscape of the system by an effective harmonic potential, and request that this potential must produce exactly the configurational temperature of the system. Due to this constraint, the force constants associated with the effective harmonic potential are increased, or equivalently, entropy of motion governed by this effective harmonic potential is reduced. We also introduce the effective configurational temperature concept which can be used as an indicator to check the anharmonicity of the free energy landscape. To validate the new method we compare it with the recently developed expansion approximate method by calculating entropy of one simple model system and two peptides with 3 and 16 amino acids either in gas phase or in explicit solvent. We show that the new method appears to be a good choice in practice as it is a compromise between accuracy and computational speed. A modification of the expansion approximate method is also introduced and advantages are discussed in some detail.
计算生物物理学和生物学的一个挑战是开发能够准确估计大分子构象熵的方法。在许多方法中，准谐近似（QH）是最广泛使用的，因为它在理论和实现上都很简单。然而，已经表明该方法对于具有崎岖自由能景观的系统来说不准确，因为它高估了熵。在这里，我们提出了一种简单的方法来改进 QH 近似，即降低 QH 熵。我们通过有效谐振子势来近似系统的势能景观，并要求该势必须精确地产生系统的构象温度。由于这种约束，与有效谐振子势相关的力常数增加，或者等效地说，由该有效谐振子势控制的运动熵降低。我们还引入了有效构象温度的概念，该概念可用作检查自由能景观的非谐性的指标。为了验证新方法，我们通过计算一个简单模型系统以及在气相或在显式溶剂中的具有 3 个和 16 个氨基酸的两个肽的熵，将其与最近开发的扩展近似方法进行了比较。我们表明，该新方法在实践中似乎是一个不错的选择，因为它在准确性和计算速度之间取得了平衡。我们还引入了扩展近似方法的修改，并详细讨论了其优点。
