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.

时间分辨吸收光谱用于研究动力学 短激光激发后蛋白质结构发生变化 脉冲。 蛋白质动力学的分子模型用于拟合和 解释测量数据。 A. 精子配体结合和构象变化的动力学 糖杯中的鲸鱼肌红蛋白已在以下温度下进行了研究 一氧化碳光解离后 100K 至 300K 血红素。 结果证实了基于 Ansari 等人的工作的预测 等人。 (1992,1994)构象松弛可以被抑制 增加溶剂粘度。 B. 折叠路径上短暂状态的动力学 细胞色素 c 已使用时间分辨吸收进行了研究 光谱学。 一氧化碳的结合破坏了折叠的稳定性 细胞色素 c 减少的状态，允许通过以下方式启动折叠 该配体的光解离。 我们观察到瞬时结合 血红素之后的其他至少两个不同的侧链 CO的光解。 C. 血红蛋白 S 的细胞内聚合动力学 研究了接受羟基脲治疗的患者的细胞。 治疗过程中延迟时间急剧增加， 治疗 12 周后中位值增加了 5 倍 24 周后增加了 10 倍以上。