Quantum Chemical Calculations of NMR Chemical Shifts in Phosphorylated Intrinsically Disordered Proteins

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14740%2F19%3A00107747" target="_blank" >RIV/00216224:14740/19:00107747 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/00216208:11160/19:10400946

Výsledek na webu

<a href="https://pubs.acs.org/doi/10.1021/acs.jctc.8b00257" target="_blank" >https://pubs.acs.org/doi/10.1021/acs.jctc.8b00257</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1021/acs.jctc.8b00257" target="_blank" >10.1021/acs.jctc.8b00257</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Quantum Chemical Calculations of NMR Chemical Shifts in Phosphorylated Intrinsically Disordered Proteins

Popis výsledku v původním jazyce

Quantum mechanics (QM) calculations are applied to examine H-1, C-13, N-15, and P-31 chemical shifts of two phosphorylation sites in an intrinsically disordered protein region. The QM calculations employ a combination of (1) structural ensembles generated by molecular dynamics, (2) a fragmentation technique based on the adjustable density matrix assembler, and (3) density functional methods. The combined computational approach is used to obtain chemical shifts (i) in the S19 and S40 residues of the non-phosphorylated and (ii) in the pS19 and pS40 residues of the doubly phosphorylated human tyrosine hydroxylase 1 as the system of interest. We study the effects of conformational averaging and explicit solvent sampling as well as the effects of phosphorylation on the computed chemical shifts. Good to great quantitative agreement with the experiment is achieved for all nuclei, provided that the systematic error cancellation is optimized by the choice of a suitable NMR standard. The effect of the standard reference on the computed N-15 and P-31 chemical shifts is demonstrated by employing three different referencing methods. Error bars associated with the statistical averaging of the computed P-31 chemical shifts are larger than the difference between the P-31 chemical shift of pS19 and pS40. The sequence trend of P-31 shifts therefore could not be reliably reproduced. On the contrary, the calculations correctly predict the change of the C-13 chemical shift for CB induced by the phosphorylation of the serine residues. The present work demonstrates that QM calculations coupled with molecular dynamics simulations and fragmentation techniques can be used as an alternative to empirical prediction tools in the structure characterization of intrinsically disordered proteins.

Název v anglickém jazyce

Quantum Chemical Calculations of NMR Chemical Shifts in Phosphorylated Intrinsically Disordered Proteins

Popis výsledku anglicky

Quantum mechanics (QM) calculations are applied to examine H-1, C-13, N-15, and P-31 chemical shifts of two phosphorylation sites in an intrinsically disordered protein region. The QM calculations employ a combination of (1) structural ensembles generated by molecular dynamics, (2) a fragmentation technique based on the adjustable density matrix assembler, and (3) density functional methods. The combined computational approach is used to obtain chemical shifts (i) in the S19 and S40 residues of the non-phosphorylated and (ii) in the pS19 and pS40 residues of the doubly phosphorylated human tyrosine hydroxylase 1 as the system of interest. We study the effects of conformational averaging and explicit solvent sampling as well as the effects of phosphorylation on the computed chemical shifts. Good to great quantitative agreement with the experiment is achieved for all nuclei, provided that the systematic error cancellation is optimized by the choice of a suitable NMR standard. The effect of the standard reference on the computed N-15 and P-31 chemical shifts is demonstrated by employing three different referencing methods. Error bars associated with the statistical averaging of the computed P-31 chemical shifts are larger than the difference between the P-31 chemical shift of pS19 and pS40. The sequence trend of P-31 shifts therefore could not be reliably reproduced. On the contrary, the calculations correctly predict the change of the C-13 chemical shift for CB induced by the phosphorylation of the serine residues. The present work demonstrates that QM calculations coupled with molecular dynamics simulations and fragmentation techniques can be used as an alternative to empirical prediction tools in the structure characterization of intrinsically disordered proteins.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10403 - Physical chemistry

Projekt

Výsledek vznikl pri realizaci vícero projektů. Více informací v záložce Projekty.

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2019

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Chemical Theory and Computation

ISSN

1549-9618

e-ISSN

—

Svazek periodika

15

Číslo periodika v rámci svazku

10

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

17

Strana od-do

5642-5658

Kód UT WoS článku

000489678700041

EID výsledku v databázi Scopus

2-s2.0-85072993684