Multiscale NMR calculations of spin-spin couplings and the
phophprylation induced chemical shifts changes in disordered
proteins

a 2022

Multiscale NMR calculations of spin-spin couplings and the phophprylation induced chemical shifts changes in disordered proteins

GAFFOUR, Amina, Vojtěch ZAPLETAL, Krishnendu BERA and Jana PAVLÍKOVÁ PŘECECHTĚLOVÁ

Basic information

Original name

Multiscale NMR calculations of spin-spin couplings and the phophprylation induced chemical shifts changes in disordered proteins

Authors

GAFFOUR, Amina, Vojtěch ZAPLETAL, Krishnendu BERA and Jana PAVLÍKOVÁ PŘECECHTĚLOVÁ

Edition

International Society of Quantum Biology and Pharmacology (ISQBP), 2022

Other information

Type of outcome

Konferenční abstrakt

Confidentiality degree

není předmětem státního či obchodního tajemství

Abstract

V originále

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.

Citovat

GAFFOUR, Amina, Vojtěch ZAPLETAL, Krishnendu BERA and Jana PAVLÍKOVÁ PŘECECHTĚLOVÁ. Multiscale NMR calculations of spin-spin couplings and the phophprylation induced chemical shifts changes in disordered proteins. In International Society of Quantum Biology and Pharmacology (ISQBP). 2022.

@proceedings{2217645,
   author = {GAFFOUR, Amina and Zapletal, Vojtěch and Bera, Krishnendu and PAVLÍKOVÁ PŘECECHTĚLOVÁ, Jana},
   booktitle = {International Society of Quantum Biology and Pharmacology (ISQBP)},
   title = {Multiscale NMR calculations of spin-spin couplings and the phophprylation induced chemical shifts changes in disordered proteins},
   year = {2022}
}

TY  - CONF
ID  - 2217645
AU  - GAFFOUR, Amina - Zapletal, Vojtěch - Bera, Krishnendu - PAVLÍKOVÁ PŘECECHTĚLOVÁ, Jana
PY  - 2022
TI  - Multiscale NMR calculations of spin-spin couplings and the phophprylation induced chemical shifts changes in disordered proteins
N2  - 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.
ER  -

GAFFOUR, Amina, Vojtěch ZAPLETAL, Krishnendu BERA and Jana PAVLÍKOVÁ PŘECECHTĚLOVÁ. Multiscale NMR calculations of spin-spin couplings and the phophprylation induced chemical shifts changes in disordered proteins. In \textit{International Society of Quantum Biology and Pharmacology (ISQBP)}. 2022.

Detailed Information on Publication Record