Resolving Dynamics in the Ensemble: Finding Paths through Intermediate States and Disordered Protein Structures.
Resolving Dynamics in the Ensemble: Finding Paths through Intermediate States and Disordered Protein Structures.
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DOI：
10.1021/acs.jpcb.1c05820
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发表时间：
2021-11-18
影响因子：
3.3
通讯作者：
Kohlstedt, Kevin L.
中科院分区：
文献类型：
--
作者：
Nijhawan, Adam K.;Chan, Arnold M.;Hsu, Darren J.;Chen, Lin X.;Kohlstedt, Kevin L.
人们发现蛋白质存在于多种多样的三维结构中。控制结构之间蛋白质相互转化的动力学发生在很宽的时间尺度范围内——从皮秒到秒。我们对蛋白质功能和动力学的理解很大程度上依赖于我们阐明物理填充结构的能力。从实验结构表征的角度来看，我们通常局限于测量稳态和时间分辨状态下的系综平均结构。生成动力学模型和理解蛋白质结构-功能关系需要对整体中填充状态的原子知识。从这个角度来看，我们提出了集成改进方法，将时间分辨实验信号与分子动力学模型相结合。我们首先讨论了无序蛋白质系统中分子模型的实验结构约束的集成，这些模型遵循最大熵原理来创建一套完整的系综结构。然后，我们提出了寻找精细结构之间的动力学途径的策略，使用时间分辨输入来指导分子动力学轨迹，并使用推理来生成定制的刺激来准备所需的蛋白质状态集合。
Proteins have been found to inhabit a diverse set of three-dimensional structures. The dynamics that govern protein interconversion between structures happen over a wide range of time scales—picoseconds to seconds. Our understanding of protein functions and dynamics is largely reliant upon our ability to elucidate physically populated structures. From an experimental structural characterization perspective, we are often limited to measuring the ensemble-averaged structure both in the steady-state and time-resolved regimes. Generating kinetic models and understanding protein structure–function relationships require atomistic knowledge of the populated states in the ensemble. In this Perspective, we present ensemble refinement methodologies that integrate time-resolved experimental signals with molecular dynamics models. We first discuss integration of experimental structural restraints to molecular models in disordered protein systems that adhere to the principle of maximum entropy for creating a complete set of ensemble structures. We then propose strategies to find kinetic pathways between the refined structures, using time-resolved inputs to guide molecular dynamics trajectories and the use of inference to generate tailored stimuli to prepare a desired ensemble of protein states.
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DOI：
10.1016/j.saa.2017.01.069
发表时间：
2017-05-05
期刊：
Spectrochimica acta. Part A, Molecular and biomolecular spectroscopy
影响因子：
--
作者：
Davis CM;Reddish MJ;Dyer RB
通讯作者：
Dyer RB
影响因子：
48
作者：
Cammarata, Marco;Levantino, Matteo;Schotte, Friedrich;Anfinrud, Philip A.;Ewald, Friederike;Choi, Jungkweon;Cupane, Antonio;Wulff, Michael;Ihee, Hyotcherl
通讯作者：
Ihee, Hyotcherl
影响因子：
2.7
作者：
Crehuet R;Buigues PJ;Salvatella X;Lindorff-Larsen K
通讯作者：
Lindorff-Larsen K
影响因子：
15
作者：
Bhowmick A;Brookes DH;Yost SR;Dyson HJ;Forman-Kay JD;Gunter D;Head-Gordon M;Hura GL;Pande VS;Wemmer DE;Wright PE;Head-Gordon T
通讯作者：
Head-Gordon T
影响因子：
7.4
作者：
Calvey, George D.;Katz, Andrea M.;Pollack, Lois
通讯作者：
Pollack, Lois