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.

该副本是利用资源的众多研究子项目之一 由NIH/NCRR资助的中心赠款提供。对该子弹的主要支持 而且，副投影的主要研究员可能是其他来源提供的 包括其他NIH来源。 列出的总费用可能 代表subproject使用的中心基础架构的估计量， NCRR赠款不直接向子弹或副本人员提供的直接资金。 这项理论研究旨在解释在电子捕获解离（ECD）条件下，各种寡糖 - 金属复合物离子的碎裂行为。更好地理解碎裂机制将有助于建立一种可靠的质谱法来实现寡糖的结构表征。 由于异构体的复杂性和少量寡糖的较大尺寸，实际上禁止了第一个原理对实际寡糖系统的ECD过程的直接理论方法。目前，该研究在两个方面进行： 1）使用分子动力学（MD）模拟技术测定寡糖的能量优选的金属结合位点。 由于电子捕获可能会在金属阳离子附近发生，因此ECD碎片模式有望受到金属结合位点的严重影响。 MD模拟是对大型柔性生物分子进行构象空间采样的有用工具。在这项研究中，使用Accelrys开发的Discoverio Studio软件通过应用CHARMM力场进行MD模拟。我们已经确定了Maltohexaose-Ca2+复合物的一些低能构象体，其中钙阳离子与几种空间相邻的氧或CH2OH组结合。目前正在研究链接和异型/异构异构体中的结合位点变化。 2）模型寡糖系统的ECD的机械研究。 根据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配合物的模型系统，并将执行高水平和密度的基于功能理论的分子轨道计算，以阐明ECD机制。 这些计算将使用波士顿大学（IBM Pseries群集和IBM BladeCenter）的超级计算设施，使用高斯03量子化学代码进行。 2010-2011期间的更新可以在“ subproject Progress”部分中找到。