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تسجيل مستخدم جديدProtein Structure Determination Using Chemical Shifts
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تأليف
Anders S. Christensen
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In this PhD thesis, a novel method to determine protein structures using chemical shifts is presented.
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We present the ProCS method for the rapid and accurate prediction of protein backbone amide proton chemical shifts - sensitive probes of the geometry of key hydrogen bonds that determine protein structure. ProCS is parameterized against quantum mecha
nical (QM) calculations and reproduces high level QM results obtained for a small protein with an RMSD of 0.25 ppm (r = 0.94). ProCS is interfaced with the PHAISTOS protein simulation program and is used to infer statistical protein ensembles that reflect experimentally measured amide proton chemical shift values. Such chemical shift-based structural refinements, starting from high-resolution X-ray structures of Protein G, ubiquitin, and SMN Tudor Domain, result in average chemical shifts, hydrogen bond geometries, and trans-hydrogen bond (h3JNC) spin-spin coupling constants that are in excellent agreement with experiment. We show that the structural sensitivity of the QM-based amide proton chemical shift predictions is needed to refine protein structures to this agreement. The ProCS method thus offers a powerful new tool for refining the structures of hydrogen bonding networks to high accuracy with many potential applications such as protein flexibility in ligand binding.
This report covers the development of a new, fast method for calculating the backbone amide proton chemical shifts in proteins. Through quantum chemical calculations, structure-based forudsiglese the chemical shift for amidprotonen in protein has bee
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