Modeling of kinetic processes in biological systems

生物系统动力学过程建模

• 批准号: 8565489
• 负责人: Alexander Berezhkovskii
• 金额: $ 5.53万
• 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/8565489
• 关键词: Accounting; Affinity; Anthrax disease; 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; Length; Ligands; Measurement; Modeling; Process; Proteins; 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 the character of folding kinetics depends on the chain length of the protein. 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.

网状蛋白包裹的囊泡的组装。我们研究了笼状蛋白包衣小孔形成的动力学，目的是合理地解释货物在囊泡形成中的作用。 通道促进的膜转运。我们研究的理论将使人们能够分析多电荷高亲和力毒素抑制剂阻断炭疽菌通道的数据，并提取关于阻滞剂与通道相互作用的信息。 用细胞表面受体测量配基浓度。我们发展了测量过程的一般理论，表明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。 果蝇胚胎中形态原梯度的形成。将我们的局部积累时间理论推广到形态原降解的非线性动力学情况，建立了局部积累时间与形态分子从源到观察点的首次通过时间之间的关系。 蛋白质折叠。我们发展了一种理论，表明折叠动力学的特征如何取决于蛋白质的链长。 复杂环境下的运输。用布朗动力学模拟方法研究了颗粒在不同形状管内的有效迁移率和扩散系数与驱动力的关系。我们的结果表明，这种依赖关系可能会因管的形状和熵陷阱的不同而有质的不同。 被一簇簇的吸收盘所捕获。我们提出了一种通过吸收盘簇捕获粒子的一般方法，该方法考虑了扩散粒子的盘片的完备性。利用这种方法，我们得到了表征由相同圆盘组成的团簇捕获的速率常数的一般公式，这些团簇的中心占据了三角形晶格的相邻位置。