New Algorithms and Software for Mass Spectrometric Analysis of Intact Proteins and Complexes

Project SummaryIntact proteins and multi protein complexes represent two of the most important levels of organization in biologyyet these levels are also some of the most difficult to studyTop down proteomics offers a bold visiondirect observationidentificationand relative quantification of all the protein forms in a biological sampleNative mass spectrometry aims at the next higher level of organization by providing a means to observe proteins in complex with ligands or other proteinsThe proposed project will build new algorithms and software for intactnativeand top down mass spectrometrySpecificallythe project will further develop Protein Metrics Intact Mass chargedeconvolution softwareincorporating multiple information channelsisotope spacingco elutionand charge statesinto the core algorithmso that the algorithm can handle complexlow signalto noise mass spectra over a wide range of masses and abundancesThe project will also build differential quantificationproteoform profilingfor undigested proteins and complexesregardless of whether or not the molecules have isotope resolutionThe project will enable a number of interesting applicationsincluding biomarker discoverylarge molecule drug comparabilitypharmacokineticsand proteinligand and proteinprotein binding Project Narrative We propose to develop commercial software products for determination of the masses of intact proteins and protein complexesand accurate comparison of these masses across samplesThe proposed project has the potential for great impact on human health in areas such as drug and vaccine development and therapeutic protein characterization