Harvard-MIT Division of Health Sciences and Technology and the Broad Institute of MIT and Harvard , Massachusetts Institute of Technology , Cambridge , Massachusetts 02139 , United States.
J Phys Chem B. 2019 Apr 4;123(13):2792-2800. doi: 10.1021/acs.jpcb.8b12517. Epub 2019 Mar 4.
Many instances of cellular signaling and transcriptional regulation involve switch-like molecular responses to the presence or absence of input ligands. To understand how these responses come about and how they can be harnessed, we develop a statistical mechanical model to characterize the types of Boolean logic that can arise from allosteric molecules following the Monod-Wyman-Changeux (MWC) model. Building upon previous work, we show how an allosteric molecule regulated by two inputs can elicit AND, OR, NAND, and NOR responses but is unable to realize XOR or XNOR gates. Next, we demonstrate the ability of an MWC molecule to perform ratiometric sensing-a response behavior where activity depends monotonically on the ratio of ligand concentrations. We then extend our analysis to more general schemes of combinatorial control involving either additional binding sites for the two ligands or an additional third ligand and show how these additions can cause a switch in the logic behavior of the molecule. Overall, our results demonstrate the wide variety of control schemes that biological systems can implement using simple mechanisms.
许多细胞信号转导和转录调控的实例涉及到对输入配体的存在或不存在的开关式分子响应。为了理解这些响应是如何产生的，以及如何利用它们，我们开发了一个统计力学模型来描述来自于变构分子的布尔逻辑类型，这些变构分子遵循 Monod-Wyman-Changeux (MWC) 模型。在以前工作的基础上，我们展示了如何通过两个输入调节变构分子可以产生 AND、OR、NAND 和 NOR 响应，但无法实现异或或同或门。接下来，我们演示了 MWC 分子进行比感测的能力——一种响应行为，其中活性取决于配体浓度比的单调性。然后，我们将我们的分析扩展到涉及两个配体的额外结合位点或额外的第三个配体的更一般的组合控制方案，并展示了这些添加如何导致分子逻辑行为的转变。总的来说，我们的结果表明，生物系统可以使用简单的机制实现各种控制方案。
