TY - JOUR

T1 - Predicting the PARP1 Tertiary Structure by Molecular Modeling Methods

AU - Mustaev, E. A.

AU - Khamitov, E. M.

N1 - This work was partially funded by the Ministry of Science and Higher Education of the Russian Federation within the State Assignment for Synchrotron Radiation Facility–Siberian Circular Photon Source “SKlF” of the Boreskov Institute of Catalysis, Siberian Branch, Russian Academy of Sciences (FWUR-2024-0040). Theoretical calculations (molecular dynamics of AF2–Zn and RF–Zn structures, MD trajectory analysis) were performed within the State Assignment of the Ministry of Science and Higher Education of the Russian Federation for Ufa Institute of Chemistry of the Ufa Federal Research Centre of the Russian Academy of Sciences No. 123011300044-5.

PY - 2025/6/2

Y1 - 2025/6/2

N2 - Abstract: A full-length tertiary structure of the poly(ADP-ribose)-polymerase 1 (PARP1) enzyme is dynamically predicted by molecular modeling methods. The prediction is performed using known tools as well as machine learning and homology construction methods. Positions of the Cα atoms of amino acid residues in the predicted structures are compared with experimentally determined geometric parameters of enzyme domains reported earlier in scientific literature and deposited to the Protein Data Bank. The obtained results can be used to make a rational choice of an appropriate prediction tool and to apply the PARP1 geometric parameters to construct dimeric forms of this enzyme and develop novel PARP1 inhibitors.

AB - Abstract: A full-length tertiary structure of the poly(ADP-ribose)-polymerase 1 (PARP1) enzyme is dynamically predicted by molecular modeling methods. The prediction is performed using known tools as well as machine learning and homology construction methods. Positions of the Cα atoms of amino acid residues in the predicted structures are compared with experimentally determined geometric parameters of enzyme domains reported earlier in scientific literature and deposited to the Protein Data Bank. The obtained results can be used to make a rational choice of an appropriate prediction tool and to apply the PARP1 geometric parameters to construct dimeric forms of this enzyme and develop novel PARP1 inhibitors.

KW - 3D protein structure prediction

KW - I-TASSER

KW - IntFOLD5, molecular dynamics

KW - PARP1, AlphaFold2, RoseTTAFold

KW - homologous construction

KW - poly(ADP-ribose)-polymerase 1

UR - https://www.mendeley.com/catalogue/bbdd0ead-270c-341a-8fdf-b23b577e729c/

UR - https://www.scopus.com/record/display.uri?eid=2-s2.0-105007019638&origin=inward&txGid=9fdcbfb66eb6b3bc65a3029a1045db9f

U2 - 10.1134/S0022476625050038

DO - 10.1134/S0022476625050038

M3 - Article

VL - 66

SP - 898

EP - 910

JO - Journal of Structural Chemistry

JF - Journal of Structural Chemistry

SN - 0022-4766

IS - 5

ER -