Modeling of kinetic processes in biological systems

生物系统动力学过程建模

• 批准号: 8941408
• 负责人: Alexander Berezhkovskii
• 金额: $ 20.09万
• 依托单位: CENTER FOR INFORMATION 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/8941408
• 关键词: Accounting; Affinity; Anthrax disease; Biological Process; Cell Surface Receptors; Cell surface; Cells; Charge; Clathrin; Clathrin-Coated Vesicles; Complex; Concentration measurement; Data Analyses; Dependence; Development; Diffuse; Diffusion; Drosophila genus; Embryo; Environment; Goals; Kinetics; Ligands; Measurement; Modeling; Probability; Process; Reaction; Role; Shapes; Site; Source; Time; Toxin; Transmembrane Transport; Tube; Vesicle; Work; biological systems; coated pit; driving force; inhibitor/antagonist; morphogens; particle; protein folding; receptor; simulation; theories

Assembly of clathrin coated vesicles. We studied the dynamics of the clathrin coated pit formation with the goal to rationalize the role of cargo in the vesicle formation. Channel-facilitated membrane transport. We worked on the theory that would allow one to analyze the data on blockage of Anthrax channel by multi-charged high-affinity toxin inhibitor, and extract the information about the blocker interaction with the channel. Ligand concentration measurements by cell surface receptors. We developed a general theory of the measurement process, which showed how the accuracy of the cell concentration measurements depends on the averaging time and the number of receptors on the cell surface. Morphogen gradient formation in the Drosophila Embryo. We generalized our theory of local accumulation time to the case of nonlinear kinetics of morphogen degradation, and established the relation between local accumulation time and the first-passage time of the morphogen molecules from the source to the observation point. Protein folding. We developed a theory that showed how one can describe protein folding using the splitting/commitment probability as a one-dimensional reaction coordinate. Transport in complex environment. Brownian dynamics simulations were used to study the dependence of the effective mobility and diffusion coefficient of a particle on the driving force in tubes of varying shape. Our results show that the dependence may be qualitatively different depending on the shapes of the tube and the entropic traps. Trapping by clusters of absorbing disks. We suggested a general approach to trapping by clusters of absorbing disks, which took into account completion of the disks for diffusing particles. Using the approach we obtained a general formula for the rate constant characterizing trapping by a cluster formed by identical disks, centers of which occupied neighboring sites of a triangular lattice.

网格蛋白包被的囊泡的组装。我们研究了网格蛋白包被的小窝形成的动力学，目的是合理化的货物在囊泡形成的作用。 凝胶促进膜转运。我们的工作理论，将允许一个分析数据的炭疽通道的多电荷的高亲和力毒素抑制剂，并提取信息的阻断剂与通道的相互作用。 通过细胞表面受体测量配体浓度。我们开发了测量过程的一般理论，该理论显示了细胞浓度测量的准确性如何取决于平均时间和细胞表面受体的数量。 果蝇胚胎中形态发生梯度的形成。我们将局部积累时间理论推广到形态发生剂降解的非线性动力学情形，建立了局部积累时间与形态发生剂分子从源到观测点的首次通过时间之间的关系. 蛋白质折叠。我们开发了一个理论，展示了如何使用分裂/承诺概率作为一维反应坐标来描述蛋白质折叠。 复杂环境下的运输。利用布朗动力学模拟方法研究了不同形状管道中粒子的有效迁移率和扩散系数对驱动力的依赖关系。我们的研究结果表明，依赖性可能是定性不同的管和熵陷阱的形状。 被一簇吸收盘捕获。我们提出了一个一般的方法来捕获集群的吸收盘，其中考虑到完成的磁盘扩散粒子。使用这种方法，我们得到了一个一般公式的速率常数表征捕获由相同的磁盘，其中心占据相邻网站的三角形晶格形成的集群。