M13生命周期的模拟I：遗传结构确定性化学动力学模拟的组装

Simulation of the M13 life cycle I: Assembly of a genetically-structured deterministic chemical kinetic simulation.

作者信息

Smeal Steven W, Schmitt Margaret A, Pereira Ronnie Rodrigues, Prasad Ashok, Fisk John D

机构信息

Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA.

Department of Chemical and Biological Engineering, Colorado State University, Fort Collins, CO 80523, USA; Department of Chemistry, Colorado State University, Fort Collins, CO 80523, USA; School of Biomedical Engineering,Colorado State University, Fort Collins, CO 80523, USA.

出版信息

Virology. 2017 Jan;500:259-274. doi: 10.1016/j.virol.2016.08.017. Epub 2016 Sep 16.

DOI:10.1016/j.virol.2016.08.017

PMID:27644585

Abstract

To expand the quantitative, systems level understanding and foster the expansion of the biotechnological applications of the filamentous bacteriophage M13, we have unified the accumulated quantitative information on M13 biology into a genetically-structured, experimentally-based computational simulation of the entire phage life cycle. The deterministic chemical kinetic simulation explicitly includes the molecular details of DNA replication, mRNA transcription, protein translation and particle assembly, as well as the competing protein-protein and protein-nucleic acid interactions that control the timing and extent of phage production. The simulation reproduces the holistic behavior of M13, closely matching experimentally reported values of the intracellular levels of phage species and the timing of events in the M13 life cycle. The computational model provides a quantitative description of phage biology, highlights gaps in the present understanding of M13, and offers a framework for exploring alternative mechanisms of regulation in the context of the complete M13 life cycle.

摘要

为了拓展对丝状噬菌体M13的定量、系统层面的理解，并促进其生物技术应用的扩展，我们已将积累的有关M13生物学的定量信息整合到一个基于遗传结构、以实验为基础的整个噬菌体生命周期的计算模拟中。确定性化学动力学模拟明确包含了DNA复制、mRNA转录、蛋白质翻译和颗粒组装的分子细节，以及控制噬菌体产生的时间和程度的竞争性蛋白质-蛋白质和蛋白质-核酸相互作用。该模拟再现了M13的整体行为，与实验报道的噬菌体种类细胞内水平值以及M13生命周期中事件的时间密切匹配。该计算模型提供了噬菌体生物学的定量描述，突出了目前对M13理解中的差距，并为在完整的M13生命周期背景下探索替代调控机制提供了一个框架。