MECHANISTIC STUDY OF ECD OF OLIGOSACCHARIDES

低聚糖ECD机理研究

• 批准号: 8365566
• 负责人: CHI-WEI LIN
• 金额: $ 5.23万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-06-01 至 2012-08-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8365566
• 关键词: Behavior; Binding; Binding Sites; Biological Models; Biology; Boston; Calcium; Cations; Code; Complex; Dissociation; Electrons; Funding; Grant; Ions; Isomerism; Mass Spectrum Analysis; Medicine; Metal Binding Site; Metals; Methods; Modeling; Molecular Conformation; National Center for Research Resources; Oligosaccharides; Oxygen; Pattern; Principal Investigator; Process; Research; Research Infrastructure; Resources; Sampling; Source; Supercomputing; System; Techniques; Theoretical Studies; United States National Institutes of Health; Universities; Update; Variant; base; conformer; cost; density; design; flexibility; metal complex; molecular dynamics; molecular orbital; quantum chemistry; software development; theories; tool

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. This theoretical study is aimed at explaining the fragmentation behavior of various oligosaccharide-metal complex ions, under electron capture dissociation (ECD) conditions. A better understanding of the fragmentation mechanism will help to establish a reliable mass spectrometric method for structural characterization of oligosaccharides. Due to the isomeric complexity and the large size of oligosaccharides, direct theoretical approach to the ECD process of actual oligosaccharide systems from first principle is practically forbidden. Currently, the research is carried out in two aspects: 1) The determination of the energetically preferred metal-binding sites for oligosaccharides, using molecular dynamics (MD) simulation techniques. Since electron capture is likely to occur near the metal cation, the ECD fragmentation pattern is expected to be heavily influenced by the metal-binding sites. MD simulation is a useful tool to perform conformation space sampling of large flexible biomolecules. In this study, MD simulation was performed by applying the CHARMm force field, using the Discovery Studio software developed by Accelrys. We have identified some low energy conformers for the maltohexaose-Ca2+ complex, where the calcium cation is bound to several spatially adjacent oxygen or CH2OH group. Binding-site variations in linkage and epimeric/anomeric isomers are currently being investigated. 2) The mechanistic study of ECD of model oligosaccharide systems. Based on the ECD results and MD simulation determined metal-oligosaccharide binding sites, model systems representing actual oligosaccharide-metal complexes will be designed and the high level ab initio- and density functional theory-based molecular orbital calculations will be performed to elucidate the ECD mechanism. These calculations will be carried out using Gaussian 03 quantum chemistry codes, utilizing the supercomputing facilities of Boston University (IBM pSeries Cluster and IBM BladeCenter). Update for the 2010-2011 period can be found in the subproject progress section.

这个子项目是许多利用资源的研究子项目之一 由NIH/NCRR资助的中心拨款提供。子项目的主要支持 而子项目的主要调查员可能是由其他来源提供的， 包括其它NIH来源。 列出的子项目总成本可能 代表子项目使用的中心基础设施的估计数量， 而不是由NCRR赠款提供给子项目或子项目工作人员的直接资金。 本理论研究的目的是解释各种寡糖-金属络合物离子的碎裂行为，在电子捕获解离（ECD）条件下。更好地了解裂解机制将有助于建立一个可靠的质谱方法，寡糖的结构表征。 由于寡糖异构体的复杂性和大尺寸，从第一原理直接理论方法到实际寡糖系统的ECD过程实际上是禁止的。目前，研究主要从两个方面展开： 1)利用分子动力学（MD）模拟技术确定寡糖的能量优先金属结合位点。 由于电子捕获可能发生在金属阳离子附近，因此预期ECD碎裂模式受到金属结合位点的严重影响。分子动力学模拟是对柔性生物大分子进行构象空间采样的有效工具。在这项研究中，MD模拟进行了应用CHARMm力场，使用Discovery Studio的软件开发的Antrys。我们已经确定了麦芽六糖-Ca 2+复合物的一些低能构象，其中钙阳离子与几个空间相邻的氧或氧离子结合。 CH 2 OH基团。目前正在研究连接和差向异构体/异头异构体的结合位点变化。 2)模型寡糖体系ECD的机理研究。 基于ECD结果和MD模拟确定的金属-寡糖结合位点，将设计代表实际寡糖-金属络合物的模型系统，并进行基于从头算和密度泛函理论的高水平分子轨道计算以阐明ECD机制。 这些计算将使用高斯03量子化学代码，利用波士顿大学的超级计算设施（IBM pSeries Cluster和IBM BladeCenter）进行。 2010-2011年期间的最新情况见次级项目进展一节。