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.
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