Verna and Marrs McLean Department of Biochemistry and Molecular Biology, Baylor College of Medicine, One Baylor Plaza Houston, Texas 77030, United States.
J Phys Chem B. 2012 Jul 26;116(29):8636-45. doi: 10.1021/jp300312u. Epub 2012 Apr 5.
In this paper, we report a novel normal-mode analysis for supramolecular complexes, named fSUB. The method models a complex as a group of flexible substructures. The low-frequency substructure modes are first determined with substructures in isolation, and the motions of the whole complex are then calculated on the basis of substructure modes and substructure-substructure interactions. The calculation of modes in fSUB requires modal analysis without initial energy minimization, which is essential for maintaining energetic and structural consistency between substructures and whole complex. Compared with other coarse-grained methods, such as the RTB method, fSUB delivers much more accurate modes for the complex and allows for the choice of much larger substructures. The method can also accommodate any type of substructure arrangement including covalent bonds across the interface. In tests on molecular chaperonin GroEL (7350 residues) and HK97 capsid complex (118,092 residues), fSUB was shown to be much more efficient in terms of combined accuracy and demand of computing resources. Our results clearly demonstrated the vital importance of including substructure flexibility in complex modal analysis, as the deformational patterns of substructures were found to play an important role even in the lowest frequency modes of the whole complex.
本文提出了一种新的超分子复合物的正则模态分析方法，命名为 fSUB。该方法将复合物建模为一组柔性子结构。首先，通过孤立的子结构确定低频子结构模态，然后根据子结构模态和子结构-子结构相互作用计算整个复合物的运动。fSUB 的模态计算需要无初始能量最小化的模态分析，这对于保持子结构和整个复合物之间的能量和结构一致性至关重要。与其他粗粒化方法（如 RTB 方法）相比，fSUB 为复合物提供了更准确的模态，并且允许选择更大的子结构。该方法还可以适应任何类型的子结构排列，包括界面处的共价键。在对分子伴侣 GroEL（7350 个残基）和 HK97 衣壳复合物（118092 个残基）的测试中，fSUB 在综合准确性和计算资源需求方面表现出更高的效率。我们的结果清楚地表明，在复合物的模态分析中包含子结构的灵活性非常重要，因为即使在整个复合物的最低频率模态中，子结构的变形模式也被发现起着重要作用。
