Nonaffine Displacements Encode Collective Conformational Fluctuations in Proteins,Journal of Chemical Theory and Computation

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Nonaffine Displacements Encode Collective Conformational Fluctuations in Proteins
Journal of Chemical Theory and Computation ( IF 5.7 ) Pub Date : 2020-03-24 , DOI: 10.1021/acs.jctc.9b01100
Dube Dheeraj Prakashchand ₁ , Navjeet Ahalawat _{1,

2} , Satyabrata Bandyopadhyay ₁ , Surajit Sengupta ₁ , Jagannath Mondal ₁

Affiliation

Identifying subtle conformational fluctuations underlying the dynamics of biomacromolecules is crucial for resolving their free energy landscape. We show that a collective variable, originally proposed for crystalline solids, is able to filter out essential macromolecular motions more efficiently than other approaches. While homogeneous or “affine” deformations of the biopolymer are trivial, biopolymer conformations are complicated by the occurrence of inhomogeneous or “nonaffine” displacements of atoms relative to their positions in the native structure. We show that these displacements encode functionally relevant conformations of macromolecules, and in combination with a formalism based upon time-structured independent component analysis, they quantitatively resolve the free energy landscape of a number of macromolecules of hierarchical complexity. The kinetics of conformational transitions among the basins can now be mapped within the framework of a Markov state model. The nonaffine modes, obtained by projecting out homogeneous fluctuations from the local displacements, are found to be responsible for local structural changes required for transitioning between pairs of macrostates.

中文翻译：

非仿射置换编码蛋白质中的总体构象波动

识别生物大分子动力学基础的细微构象波动对于解决其自由能格局至关重要。我们表明，最初为结晶固体提出的一个集体变量能够比其他方法更有效地滤除必要的大分子运动。虽然生物聚合物的均质或“仿射”形变是微不足道的，但由于原子相对于其在天然结构中的位置的不均匀或“非亲和”位移的出现，生物聚合物构象变得复杂。我们表明，这些置换编码大分子的功能相关构象，并结合基于时间结构的独立成分分析的形式主义，他们定量地解决了许多具有复杂性的大分子的自由能态。现在可以在马尔可夫状态模型的框架内绘制盆地之间构象转变的动力学。通过从局部位移中推算出均匀波动而获得的非仿射模式，被发现是在成对的大状态之间转换所需的局部结构变化的原因。

更新日期：2020-04-24

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