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

J 2019

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

PAVLÍKOVÁ PŘECECHTĚLOVÁ, Jana, Arnošt MLÁDEK, Vojtěch ZAPLETAL and Jozef HRITZ

Basic information

Original name

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

Authors

PAVLÍKOVÁ PŘECECHTĚLOVÁ, Jana (203 Czech Republic, guarantor, belonging to the institution), Arnošt MLÁDEK (203 Czech Republic, belonging to the institution), Vojtěch ZAPLETAL (203 Czech Republic, belonging to the institution) and Jozef HRITZ (703 Slovakia, belonging to the institution)

Edition

Journal of Chemical Theory and Computation, Washington DC, American Chemical Society, 2019, 1549-9618

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

10403 Physical chemistry

Country of publisher

United States of America

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.011

RIV identification code

RIV/00216224:14740/19:00107747

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1021/acs.jctc.8b00257

UT WoS

000489678700041

Keywords in English

DENSITY-FUNCTIONAL CALCULATIONS; MOLECULAR-ORBITAL METHODS; CORRELATION-ENERGY; BASIS-SET; MECHANICAL CALCULATION; PERTURBATION-THEORY; SHIELDING SCALE; AB-INITIO; P-31; N-15

Abstract

V originále

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.

Links

GF15-34684L, research and development project

Name: Efektivní výpočty volných energií a konfiguračního vzorkování protein-‐proteinových interakcí

Investor: Czech Science Foundation, Partner Agency (Austria)

LM2015085, research and development project

Name: CERIT Scientific Cloud (Acronym: CERIT-SC)

Investor: Ministry of Education, Youth and Sports of the CR, CERIT Scientific Cloud

LQ1601, research and development project

Name: CEITEC 2020 (Acronym: CEITEC2020)

Investor: Ministry of Education, Youth and Sports of the CR

Citovat

PAVLÍKOVÁ PŘECECHTĚLOVÁ, Jana, Arnošt MLÁDEK, Vojtěch ZAPLETAL and Jozef HRITZ. Quantum Chemical Calculations of NMR Chemical Shifts in Phosphorylated Intrinsically Disordered Proteins. Journal of Chemical Theory and Computation. Washington DC: American Chemical Society, 2019, vol. 15, No 10, p. 5642-5658. ISSN 1549-9618. Available from: https://dx.doi.org/10.1021/acs.jctc.8b00257.

@article{1574798,
   author = {Pavlíková Přecechtělová, Jana and Mládek, Arnošt and Zapletal, Vojtěch and Hritz, Jozef},
   article_location = {Washington DC},
   article_number = {10},
   doi = {http://dx.doi.org/10.1021/acs.jctc.8b00257},
   keywords = {DENSITY-FUNCTIONAL CALCULATIONS; MOLECULAR-ORBITAL METHODS; CORRELATION-ENERGY; BASIS-SET; MECHANICAL CALCULATION; PERTURBATION-THEORY; SHIELDING SCALE; AB-INITIO; P-31; N-15},
   language = {eng},
   issn = {1549-9618},
   journal = {Journal of Chemical Theory and Computation},
   title = {Quantum Chemical Calculations of NMR Chemical Shifts in Phosphorylated Intrinsically Disordered Proteins},
   url = {https://pubs.acs.org/doi/10.1021/acs.jctc.8b00257},
   volume = {15},
   year = {2019}
}

TY  - JOUR
ID  - 1574798
AU  - Pavlíková Přecechtělová, Jana - Mládek, Arnošt - Zapletal, Vojtěch - Hritz, Jozef
PY  - 2019
TI  - Quantum Chemical Calculations of NMR Chemical Shifts in Phosphorylated Intrinsically Disordered Proteins
JF  - Journal of Chemical Theory and Computation
VL  - 15
IS  - 10
SP  - 5642-5658
EP  - 5642-5658
PB  - American Chemical Society
SN  - 15499618
KW  - DENSITY-FUNCTIONAL CALCULATIONS
KW  - MOLECULAR-ORBITAL METHODS
KW  - CORRELATION-ENERGY
KW  - BASIS-SET
KW  - MECHANICAL CALCULATION
KW  - PERTURBATION-THEORY
KW  - SHIELDING SCALE
KW  - AB-INITIO
KW  - P-31
KW  - N-15
UR  - https://pubs.acs.org/doi/10.1021/acs.jctc.8b00257
L2  - https://pubs.acs.org/doi/10.1021/acs.jctc.8b00257
N2  - 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.
ER  -

PAVLÍKOVÁ PŘECECHTĚLOVÁ, Jana, Arnošt MLÁDEK, Vojtěch ZAPLETAL and Jozef HRITZ. Quantum Chemical Calculations of NMR Chemical Shifts in Phosphorylated Intrinsically Disordered Proteins. \textit{Journal of Chemical Theory and Computation}. Washington DC: American Chemical Society, 2019, vol.~15, No~10, p.~5642-5658. ISSN~1549-9618. Available from: https://dx.doi.org/10.1021/acs.jctc.8b00257.

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