![]() New Mechanism is often associated with the authors of a few works from the 1990s who drew attention to the centrality of the search for mechanisms in the scientific enterprise (Bechtel and Richardson 1993 Glennan 1996 Machamer et al. The term “New Mechanism” (Craver and Tabery 2019 Craver and Krickel 2019 Glennan and Illari 2018b) has proved a convenient label to refer to this research, which has emerged over the last 30 + years, but, like any philosophical ism, it can be hard to pin down. Illustration was created with TinkerCell ( ).In this paper we identify six theses that constitute core results of philosophical investigation into the nature of mechanisms and of the role that the search for and identification of mechanisms play in the sciences. This binding prevents the RNA polymerase from binding and starting the transcription process. The lac repressor binds to the operator, which is partially overlapping with the promoter region. ![]() lacI is continuously transcribed and the repressor protein is always present. LacI, the gene encoding for the lac repressor, is not part of the operon and is under the control of its own promoter. When the operon is active, the three structural genes will be produced, namely lacZ, lacY and lacA. RNA polymerase is thus free to start transcribing the operon. Allolactose binds to the lac repressor (big purple node), stabilizing a conformation unable to bind the operator (orange box with a black minus). This also happens because, as extracellular lactose (depicted with pale orange nodes) is imported into the cell, a fraction of it is converted to allolactose (green nodes). The cAMP-CAP binding favors the binding of the RNA polymerase (orange node) to the promoter (thick black arrow) site. In the absence of extracellular glucose (depicted with degradation circles), the hunger molecule cAMP (blue node) binds to CAP (green node) and stabilizes a conformation with a high affinity for the regulator CAP site of DNA (depicted with a green box with a cross). These molecules are responsible for switching the lac operon ON or OFF, depending on sugar availability. ![]() The lac operon is under the control of two regulatory molecules, the lac repressor and the CAP. See main text for details about the regulation of the lac operon. For Permissions, please email: Disclaimer In silico simulations lac operon Cell Collective GINsim computational systems biology mechanistic logic-based models. The protocol can be completed by users with little to no prior computational modeling experience approximately within 3 h. The complete modeling workflow is applied to a well-studied and familiar biological process-the lac operon regulatory system. To ensure broad accessibility of the protocol, we use a logical modeling framework, which presents a lower mathematical barrier of entry, and two easy-to-use and popular modeling software tools: Cell Collective and GINsim. ![]() The protocol provides a framework that includes defining the model scope, choosing validation criteria, selecting the appropriate modeling approach, constructing a model and simulating the model. Aimed at those who are new to computational modeling, we present here a practical hands-on protocol breaking down the process of mechanistic modeling of biological systems in a succession of precise steps. These models provide a means to analyze the dynamics of the systems they describe, and to study and interrogate their properties, and provide insights about the emerging behavior of the system in the presence of single or combined perturbations. Mechanistic computational models enable the study of regulatory mechanisms implicated in various biological processes.
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