Blinov Michael L, Schaff James C, Vasilescu Dan, Moraru Ion I, Bloom Judy E, Loew Leslie M
R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut School of Medicine, Farmington, Connecticut.
R. D. Berlin Center for Cell Analysis and Modeling, University of Connecticut School of Medicine, Farmington, Connecticut.
Biophys J. 2017 Oct 3;113(7):1365-1372. doi: 10.1016/j.bpj.2017.08.022.
In rule-based modeling, molecular interactions are systematically specified in the form of reaction rules that serve as generators of reactions. This provides a way to account for all the potential molecular complexes and interactions among multivalent or multistate molecules. Recently, we introduced rule-based modeling into the Virtual Cell (VCell) modeling framework, permitting graphical specification of rules and merger of networks generated automatically (using the BioNetGen modeling engine) with hand-specified reaction networks. VCell provides a number of ordinary differential equation and stochastic numerical solvers for single-compartment simulations of the kinetic systems derived from these networks, and agent-based network-free simulation of the rules. In this work, compartmental and spatial modeling of rule-based models has been implemented within VCell. To enable rule-based deterministic and stochastic spatial simulations and network-free agent-based compartmental simulations, the BioNetGen and NFSim engines were each modified to support compartments. In the new rule-based formalism, every reactant and product pattern and every reaction rule are assigned locations. We also introduce the rule-based concept of molecular anchors. This assures that any species that has a molecule anchored to a predefined compartment will remain in this compartment. Importantly, in addition to formulation of compartmental models, this now permits VCell users to seamlessly connect reaction networks derived from rules to explicit geometries to automatically generate a system of reaction-diffusion equations. These may then be simulated using either the VCell partial differential equations deterministic solvers or the Smoldyn stochastic simulator.
在基于规则的建模中，分子相互作用以反应规则的形式系统地指定，这些规则充当反应的生成器。这提供了一种方法来解释多价或多状态分子之间所有潜在的分子复合物和相互作用。最近，我们将基于规则的建模引入到虚拟细胞（VCell）建模框架中，允许以图形方式指定规则，并将自动生成的网络（使用BioNetGen建模引擎）与手动指定的反应网络合并。VCell为从这些网络导出的动力学系统的单室模拟提供了许多常微分方程和随机数值求解器，以及基于规则的无网络代理模拟。在这项工作中，基于规则的模型的隔室和空间建模已在VCell中实现。为了实现基于规则的确定性和随机空间模拟以及无网络的基于代理的隔室模拟，分别对BioNetGen和NFSim引擎进行了修改以支持隔室。在新的基于规则的形式体系中，为每个反应物和产物模式以及每个反应规则分配位置。我们还引入了基于规则的分子锚定概念。这确保了任何有分子锚定到预定义隔室的物种都将保留在该隔室中。重要的是，除了构建隔室模型之外，现在这还允许VCell用户将从规则导出的反应网络无缝连接到显式几何结构，以自动生成反应 - 扩散方程组。然后可以使用VCell偏微分方程确定性求解器或Smoldyn随机模拟器对这些方程组进行模拟。
