DEVELOPMENT OF A MULTI-SCALE CHEMICAL MODELING APPROACH TO HEME-CONTAINING ENZY

含血红素酶的多尺度化学建模方法的开发

• 批准号: 8171870
• 负责人: TROY WYMORE
• 金额: $ 0.14万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-08-01 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8171870
• 关键词: Active Sites; Apoptosis; Binding; Chemical Models; Complex; Computer Retrieval of Information on Scientific Projects Database; Computing Methodologies; Development; Electron Transport; Electrons; Funding; Grant; Heme; Hemeproteins; Hemoglobin; Hydrogen Peroxide; Institution; Iron; Methods; Play; Research; Research Personnel; Resources; Role; Sampling; Source; Structure; Structure-Activity Relationship; System; United States National Institutes of Health; biological systems; electronic structure; ferryl iron; molecular dynamics; molecular mechanics; oxidation; small molecule

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Iron-containing heme proteins play a central role in many biological systems; binding small molecules for transport and facilitating electron transfer and apoptosis. The apparent simplicity of their active sites makes these systems ideal for structure-function studies. Yet, they are also complicated by the existence of multiple oxidation states (FeII, the ferrous state, FeIII, the ferric state and FeIV, the ferryl ion) as well as multiple spin states. For example, the ferric Hemoglobin I upon binding hydrogen peroxide (H2O2) could exist as a doublet (one unpaired electron) or a quartet (three unpaired electrons) and may even convert between the two states as it progresses from the bound complex to compound I (the ferryl ion). Clearly, using computational methods to describe the mechanism (and hence construct a detailed structure-function relationship) will require accurate electronic structure methods. Yet, the ability to sample plausible structures besides the crystal structure is also crucial to a full understanding of such systems. The most efficient way to sample alternative structures is through simulations (molecular dynamics (MD) or Monte Carlo (MC)) that employ classical molecular mechanics (MM) force fields.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 含铁血红素蛋白在许多生物系统中发挥着核心作用。结合小分子进行运输并促进电子转移和细胞凋亡。其活性位点的明显简单性使这些系统成为结构功能研究的理想选择。 然而，它们也因多种氧化态（FeII，亚铁态，FeIII，三价铁态和 FeIV，铁离子）以及多种自旋态的存在而变得复杂。 例如，铁血红蛋白 I 在结合过氧化氢 (H2O2) 时可以作为双峰（一个不成对电子）或四峰（三个不成对电子）存在，甚至可以在从结合复合物发展到化合物 I 时在两种状态之间转换。 （费瑞尔离子）。 显然，使用计算方法来描述机制（从而构建详细的结构-功能关系）将需要精确的电子结构方法。然而，除了晶体结构之外，对合理结构进行采样的能力对于充分理解此类系统也至关重要。 对替代结构进行采样的最有效方法是通过采用经典分子力学 (MM) 力场的模拟（分子动力学 (MD) 或蒙特卡罗 (MC)）。