Core--Development of new Features in MCell

核心--MCell新功能开发

• 批准号: 7553845
• 负责人: Terrence J Sejnowksi
• 金额: $ 16.89万
• 依托单位: CALIFORNIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7553845
• 关键词: Achievement; Algorithms; Attention; Biochemical; Cell membrane; Cell physiology; Cells; Cereals; Complex; Computer-Aided Design; Computers; Cytosol; Data; Development; Diffuse; Human; Individual; Kinetics; Label; Language; Ligand Binding; Ligands; Macromolecular Complexes; Maps; Modeling; Molecular; Neurons; Neuropil; Numbers; Process; Pump; Purpose; Reaction; Scheme; Shorthand; Signal Pathway; Signal Transduction; Simulate; Specific qualifier value; Structure; Subcellular Spaces; Surface; System; Terminology; Text; To specify; Validation; calmodulin-dependent protein kinase II; cell type; computer program; density; design; programs; receptor; reconstruction; scaffold; simulation; success; three-dimensional modeling; user-friendly

Typical cellular processes occur in highly organized subcellular spaces, where ligand and ligand-binding molecules participate in complex signaling pathways. In general, then, it is not sufficient to consider molecular signals, such as the intracellular Ca 2+ concentration, only in well-mixed whole cell terms, but instead attention must center on the relevant subcellular microdomains. The number of signaling and effector molecules can be quite small, and computers have become powerful enough so that it is now feasible to simulate every important molecule in subcellular regions. MCell is a general computer program designed to simulate microdomains and associated biochemical signaling mechanisms. The specific aims of this core will add new capabilities to MCell that will streamline the process of mapping molecules and macromolecular complexes into realistic three-dimensional reconstructions of cellular ultrastructure and will implement algorithms for simulating interactions between diffusing molecules. The first specific aim is to design algorithms to permit simulation of all possible pair-wise interactions between diffusing molecules, which will allow simulation of cytosolic signal transduction cascades within MCelI. The second specific aim is to develop a user-friendly cellular computer-assisted design (CAD) system for use with the MCell program. The cellular CAD system will allow graphical design of realistic models of neurons and other cell types at the subcellular and molecular level and to rapidly populate surfaces with channels, pumps and other molecules at specified densities. The third specific aim is to design algorithms to streamline the representation of macromolecular complexes and reaction networks. This will involve the development of a high-level and hierarchical representation language for reaction networks that will provide a convenient, machine readable, shorthand for representing complex reaction networks. This proposed MCell development will also allow the user to specify the level of coarse-graining by letting the label structure specifying the internal states of reactants to be defined as needed for specific applications. These new modeling capabilities for MCell are prerequisite for the success of Project 1 (Sejnowski) and Project 3 (Kennedy) in this proposal and will facilitate the integration of experimental data from Project 2 (Weinberg) and Project 4 (Svoboda) into MCell simulations.

典型的细胞过程发生在高度组织化的亚细胞空间中，其中配体和配体结合分子参与复杂的信号传导途径。因此，一般来说，仅仅考虑分子信号（如细胞内Ca 2+浓度）是不够的，而必须将注意力集中在相关的亚细胞微区。信号分子和效应分子的数量可以很小，而计算机已经变得足够强大，因此现在可以模拟亚细胞区域中的每一个重要分子。MCell是一个通用的计算机程序，旨在模拟微区和相关的生化信号机制。的具体目标 该核心将为MCell增加新的能力，使分子和大分子复合物映射成细胞超微结构的真实三维重建的过程流线化，并将实现用于模拟扩散分子之间相互作用的算法。第一个具体目标是设计算法，允许模拟扩散分子之间所有可能的成对相互作用，这将允许模拟MCel I内的胞质信号转导级联。第二个具体目标是开发一个用户友好的蜂窝计算机辅助设计（CAD）系统与MCell程序使用。 细胞CAD系统将允许神经元和其他细胞类型的真实模型的图形设计， 亚细胞和分子水平，并以特定密度用通道、泵和其它分子快速填充表面。第三个具体目标是设计算法来简化大分子复合物和反应网络的表示。这将涉及一个高层次的反应网络，将提供一个方便的，机器可读的，速记表示复杂的反应网络的分层表示语言的发展。该建议的MCell开发还将允许用户指定粗粒化的水平，方法是根据特定应用的需要定义指定反应物内部状态的标签结构。MCell的这些新建模功能包括 这是项目1（Sejnowski）和项目3（Kennedy）在本提案中成功的先决条件，并将促进项目2（温伯格）和项目4（Svoboda）的实验数据整合到MCell模拟中。