MACROMOLECULAR DYNAMICS AND ASSEMBLY REACTIONS

大分子动力学和组装反应

• 批准号: 3754171
• 负责人: J HOFRICHTER
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES
• 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/3754171
• 关键词: biophysics; blood disorder chemotherapy; carbon monoxide; chemical association; chemical binding; chemical kinetics; chemical models; conformation; cytochrome c; heme; hemoglobin Ss; hemoprotein structure; hydroxyurea; laser spectrometry; molecular dynamics; myoglobin; photochemistry; photolysis; polymerization; protein folding; sickle cell anemia; sickling inhibitor; time resolved data; viscosity

Time-resolved absorption spectroscopy is used to study the dynamics of protein structural changes subsequent to excitation with short laser pulses. Molecular models for the protein dynamics are used to fit and interpret the measured data. A. The kinetics of ligand binding and conformational changes for sperm whale myoglobin in sugar glasses have been studied at temperatures from 100K to 300 K following the photodissociation of carbon monoxide from the hemes. The results confirm the prediction, based on work of Ansari et al. (1992,1994) that conformational relaxation can be inhibited by increasing the solvent viscosity. B. The dynamics of short-lived states on the folding pathway of cytochrome c have been investigated using time-resolved absorption spectroscopy. The binding of carbon monoxide destabilized the folded state of reduced cytochrome c, permitting folding to be initiated by photodissociation of this ligand. We have observed transient binding of other at least two different side chains to the heme subsequent to photodissociation of CO. C. The kinetics of intracellular polymerization of hemoglobin S have been studied for cells from patients undergoing treatment with hydroxyurea. The delay times increased dramatically in the course of treatment, with the median value increased by a factor of 5 after 12 weeks of treatment and more than a factor of 10 after 24 weeks.

时间分辨的吸收光谱用于研究 蛋白质结构变化在激发短激光之后发生 脉冲。 蛋白质动力学的分子模型用于拟合和 解释测量数据。 答：精子的配体结合和构象变化的动力学 在温度下研究了糖眼镜中的鲸鱼肌红蛋白 一氧化碳从 下摆。 结果基于Ansari et的工作证实了预测 al。 （1992年，1994年），可以抑制构象放松 增加溶剂粘度。 B.短暂状态在折叠途径上的动态 已经使用时间分辨吸收研究了细胞色素C 光谱法。 一氧化碳的结合破坏了折叠 细胞色素C的降低状态，允许折叠起来 该配体的光解离。 我们已经观察到了瞬时结合的 在此之后的其他至少两个不同的血红素的侧链 Co的光解离 C.血红蛋白的细胞内聚合的动力学已是 研究了接受羟基脲治疗患者的细胞。 在治疗过程中，延迟时间急剧增加， 治疗12周后，中值增加了5倍 24周后超过10倍。