Speakers
Description
Computed chemical shifts (CSs) enable experimentalists to determine the ensemble of structures that reflect the flexibility of intrinsically disordered proteins (IDPs) and that are in accordance with experimental nuclear magnetic resonance (NMR) data. The reliable calculation or prediction of CSs is therefore a prerequisite for a successful structure characterization of phosphorylated IDPs that regulate a vast range of processes leading to neurodegenerative diseases.
The calculation of CSs by quantum chemistry methods poses many challenges that stem from the flexibility and complexity of IDPs as well as from methodological limitations or referencing problems. We will present our quest for the design of a multiscale computational protocol that builds on the combination of (i) structural ensembles generated by molecular dynamics, (ii) a fragmentation technique based on the adjustable density matrix assembler, and (iii) density functional methods.
We will demonstrate the effects of conformational averaging, explicit solvent sampling, statistical sample size as well as the effects of a basis set and phosphorylation on the computed CSs. Our results indicate that good to great quantitative agreement with experiment is achieved for all nuclei provided that the systematic error is balanced by the choice of a suitable NMR standard. The poster presentation will reflect on the potential of the computational protocol to serve as an alternative to empirical prediction tools in the structure characterization of IDPs by NMR spectroscopy.
