CONFORMATION AND ELECTRONIC STRUCTURE OF BIOLOGICAL MOLECULES

生物分子的构象和电子结构

• 批准号: 3917721
• 负责人: W A EATON
• 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/3917721
• 关键词: Raman spectrometry; atomic absorption spectrometry; binding proteins; birefringences; carbon monoxide; chemical structure function; conformation; dichroism; heme; hemoglobin; hemoprotein structure; laser spectrometry; ligands; photolysis; quantum chemistry

Time resolved optical spectroscopy with nanosecond lasers and molecular dynamics calcularions have been employed to investigate ligand rebinding and conformational changes in hemoglobin subsequent to photodissociation of the carbon monoxide complex. In order to precisely measure the time course of the changes in the conformation of the deoxy photoproduct, which produce small spectral changes, as well as to determine the kinetics of ligand rebinding, an automated, sensitive nanosecond specrrometer has been developed to measure time-resoved spectra. The spectra have been anaylzed using singular value decomposition to produce a set of orthonormal basis spectra and the time course of their amplitudes. With these techniques the kinetics of ligand rebinding and con- formational changes have been studied with hemoglobins initially in the R and T quaternary structure. The R to T quaternary transition is observed for the completely unliganded R state molecule to occur at about 20 &m&s, while both R and T state molecules show tertiary conformational relaxations at about 50 ns and 500 ns. The 50 ns relaxation is simultaneous with geminate rebinding, suggesting that it is caused by motion of the ligand out of the heme pocket. Using the simplest kinetic model, a comparison of the geminate kinetics for R and T state molecules indicate that the difference in the factor of about 50 in the overall rate of ligand binding to the R and T states can be explained by differences in binding rates to the heme from within the heme pocket. Changes in the barriers to motion of the

时间通过纳秒激光解析光谱法和 分子动力学已用于研究 血红蛋白的配体重新固定和构象变化 后来进行一氧化碳复合物的光解离。 为了精确衡量变化的时间过程 脱氧光生的构象，产生小 光谱变化，并确定配体的动力学 重新启动，自动化，敏感的纳秒规格计一直是 开发用于测量时间恢复的光谱。 光谱已经 使用单数值分解来产生一组 正顺序基谱及其幅度的时间过程。 借助这些技术，配体重新固定和构的动力学 最初用血红蛋白研究了形成性变化 在r和t季前结构中。 r到t quaternary 观察到完全非配置的R状态的过渡 分子发生在大约20＆m＆s，而R和T状态都发生 分子在大约50 ns处显示三级构象放松 和500 ns。 50 NS放松与Geminate同时发生 重新固定，表明它是由配体的运动引起的 血红素口袋。 使用最简单的动力学模型，比较 R和T状态分子的Geminate动力学表明 总体速率约为50的因素的差异 配体与R和T状态的结合可以通过 血红素内与血红素的结合速率差异 口袋。 运动障碍的变化