NERDSS: A Nonequilibrium Simulator for Multibody Self-Assembly at the Cellular Scale.
NERDSS: A Nonequilibrium Simulator for Multibody Self-Assembly at the Cellular Scale.
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NERDSS：细胞尺度多体自组装的非平衡模拟器。
DOI：
10.1016/j.bpj.2020.05.002
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发表时间：
2020
影响因子：
3.4
通讯作者：
Johnson,MargaretE
中科院分区：
文献类型：
--
作者：
Varga,MatthewJ;Fu,Yiben;Loggia,Spencer;Yogurtcu,OsmanN;Johnson,MargaretE
目前，建立细胞自组装过程的预测模型的一个重要障碍是，分子模型不能捕获将不同组分与活性过程耦合的分钟长的动力学，而反应扩散模型不能捕获分子组装的结构。在这里，我们介绍了非平衡反应扩散自组装模拟器（NERDSS），它解决了这个时空分辨率差距。NERDSS将高效的反应扩散算法集成到通用软件中，该软件通过扩散、结合和定向、解结合、化学转化和空间定位对用户定义的分子进行操作。通过将快速结合过程与大规模组装的缓慢时间尺度相连接，NERDSS将分子解析与有序多亚基复合物的可逆形成相结合。NERDSS使用基于规则的格式化语言对模型进行编码，以促进模型的可移植性、可用性和可再现性。将NERDSS应用于网格蛋白介导的内吞作用中的步骤，我们设计了可以在溶液中或膜上形成晶格的多组分系统，并且我们预测了膜脂质的随机但局部去磷酸化如何驱动晶格解体。NERDSS模拟揭示了晶格生长的空间约束和成核组装中膜定位和协同性的作用。通过模拟病毒晶格组装和重演生物钟模型的蛋白质表达水平的振荡，我们说明了NERDSS的适应性。NERDSS模拟了用户定义的组装模型，这些模型以前无法使用现有的软件工具，广泛应用于预测体内自组装和设计体外高产组装。
Currently, a significant barrier to building predictive models of cellular self-assembly processes is that molecular models cannot capture minutes-long dynamics that couple distinct components with active processes, whereas reaction-diffusion models cannot capture structures of molecular assembly. Here, we introduce the nonequilibrium reaction-diffusion self-assembly simulator (NERDSS), which addresses this spatiotemporal resolution gap. NERDSS integrates efficient reaction-diffusion algorithms into generalized software that operates on user-defined molecules through diffusion, binding and orientation, unbinding, chemical transformations, and spatial localization. By connecting the fast processes of binding with the slow timescales of large-scale assembly, NERDSS integrates molecular resolution with reversible formation of ordered, multisubunit complexes. NERDSS encodes models using rule-based formatting languages to facilitate model portability, usability, and reproducibility. Applying NERDSS to steps in clathrin-mediated endocytosis, we design multicomponent systems that can form lattices in solution or on the membrane, and we predict how stochastic but localized dephosphorylation of membrane lipids can drive lattice disassembly. The NERDSS simulations reveal the spatial constraints on lattice growth and the role of membrane localization and cooperativity in nucleating assembly. By modeling viral lattice assembly and recapitulating oscillations in protein expression levels for a circadian clock model, we illustrate the adaptability of NERDSS. NERDSS simulates user-defined assembly models that were previously inaccessible to existing software tools, with broad applications to predicting self-assembly in vivo and designing high-yield assemblies in vitro.