Publication details
Multiscale NMR calculations of spin-spin couplings and the phophprylation induced chemical shifts changes in disordered proteins
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| Year of publication | 2022 |
| Type | Conference abstract |
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| Description | Intrinsically disordered proteins (IDPs) are post-translationally modified polypeptide chains that fail to form a stable single well-defined three-dimensional (3D) structure. These proteins are crucial for understanding the progression of neurodegenerative diseases such as Alzheimer and Parkinson. Despite their unstable structure, they serve an important function in a variety of processes, including molecular recognition and the regulation of transcription. Both NMR experiment interpretations and computational approaches are used to characterize the structural properties of IDPs. The aim of our work is to design a reliable multiscale protocol for the calculation of NMR spectroscopy parameters in IDPs. We use (1) the Map2c protein fragment consisting of residues (159-245) to compute 1H, 13C and 15N NMR chemical shifts and the (2) Tau(210-240) protein frgament to calculate 3JHN-Ha spin-spin couplings for this purpose. To obtain the NMR parameters, we designed a computational protocol that combines classical molecular dynamics and density functional caluclations.. We use the MD trajectory to construct structural ensembles that represent the IDP conformational space. Prior to the NMR calculations, all ensemble structures are subject to protein fragmentation in order to constract molecular clusters that are computationally feasible. In particular, we apply the fragmentation by the Adjustable Density Matrix Assembler that splits a protein into individual aminoacids and further into their backbone and side chain parts. The resulting fragments are embedded in the protein surroundings including the ions and explicit solvent. In the poster contribution, we will demonstrate the performance of MD/DFT calculations for NMR chemical shifts in both phosphorylated and non-phosphorylated Map2c. Additionally, we will compare the calculated spin-spin couplings with the experimental data and with empirically derived predictions based on Karplus equations for Tau proteins. |