Nguyen Phuong H, Mu Yuguang, Stock Gerhard
Institute of Physical and Theoretical Chemistry, J. W. Goethe University, Frankfurt, Germany.
Proteins. 2005 Aug 15;60(3):485-94. doi: 10.1002/prot.20485.
A replica exchange molecular dynamics (REMD) simulation of a bicyclic azobenzene peptide in explicit dimethyl sulfoxide solution is presented in order to characterize the conformational structures and energy landscape of a photoswitchable peptide. It is shown that an enhanced-sampling technique such as the REMD method is essential to obtain a converged conformational sampling of the peptide at room temperature. This is because conventional MD simulations of less than approximately 100-ns length are either trapped in local minima (at 295 K) or-if run at high temperature-do not resemble the room-temperature REMD results. Calculating various nuclear Overhauser effects (NOEs) and (3)J-couplings, a good overall agreement between the REMD simulations and the NMR experiments of Renner et al. (Biopolymers 2000;54:501-514) is found. In particular, the REMD study confirms the general picture drawn by Renner et al. that the trans-isomer of the azobenzene peptide exhibits a well-defined structure, while the cis-isomer is a conformational heterogeneous system; that is, the trans-isomer occurs in 2 well-defined conformers, while the cis-isomer represents an energetically frustrated system that leads to an ensemble of conformational structures. Employing a principal component analysis of the REMD data, the free energy landscape of the systems is studied at various temperatures. The implications for the folding and unfolding pathways of the system are discussed.
本文展示了在明确的二甲基亚砜溶液中对双环偶氮苯肽进行的复制交换分子动力学（REMD）模拟，以表征光开关肽的构象结构和能量景观。结果表明，诸如REMD方法之类的增强采样技术对于在室温下获得肽的收敛构象采样至关重要。这是因为长度小于约100纳秒的传统分子动力学模拟要么被困在局部最小值（在295 K时），要么在高温下运行时与室温下的REMD结果不同。通过计算各种核Overhauser效应（NOE）和（3）J耦合，发现REMD模拟与Renner等人的核磁共振实验（《生物聚合物》2000年；54：501 - 514）总体上有很好的一致性。特别是，REMD研究证实了Renner等人所描绘的总体情况，即偶氮苯肽的反式异构体具有明确的结构，而顺式异构体是构象异质体系；也就是说，反式异构体以2种明确的构象存在，而顺式异构体代表一个能量受挫的体系，导致构象结构的集合。通过对REMD数据进行主成分分析，研究了该系统在不同温度下的自由能景观。讨论了对该系统折叠和展开途径的影响。
