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Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors.
J Recept Signal Transduct Res. 2014 Oct; 34(5):417-30.JR

Abstract

Poly(ADP-ribose) polymerase-1 (PARP-1) functions as a DNA damage sensor and signaling molecule. It plays a vital role in the repair of DNA strand breaks induced by radiation and chemotherapeutic drugs; inhibitors of this enzyme have the potential to improve cancer chemotherapy or radiotherapy. Three-dimensional quantitative structure activity relationship (3D QSAR) models were developed using comparative molecular field analysis, comparative molecular similarity indices analysis and docking studies. A set of 88 molecules were docked into the active site of six X-ray crystal structures of poly(ADP-ribose)polymerase-1 (PARP-1), by a procedure called multiple receptor conformation docking (MRCD), in order to improve the 3D QSAR models through the analysis of binding conformations. The docked poses were clustered to obtain the best receptor binding conformation. These dock poses from clustering were used for 3D QSAR analysis. Based on MRCD and QSAR information, some key features have been identified that explain the observed variance in the activity. Two receptor-based QSAR models were generated; these models showed good internal and external statistical reliability that is evident from the [Formula: see text], [Formula: see text] and [Formula: see text]. The identified key features enabled us to design new PARP-1 inhibitors.

Authors+Show Affiliations

Department of Chemistry, University College of Science, Osmania University , Hyderabad, Andhra Pradesh , India.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25046176

Citation

Fatima, Sabiha, et al. "Multiple Receptor Conformation Docking, Dock Pose Clustering and 3D QSAR Studies On Human poly(ADP-ribose) Polymerase-1 (PARP-1) Inhibitors." Journal of Receptor and Signal Transduction Research, vol. 34, no. 5, 2014, pp. 417-30.
Fatima S, Jatavath MB, Bathini R, et al. Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. J Recept Signal Transduct Res. 2014;34(5):417-30.
Fatima, S., Jatavath, M. B., Bathini, R., Sivan, S. K., & Manga, V. (2014). Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. Journal of Receptor and Signal Transduction Research, 34(5), 417-30. https://doi.org/10.3109/10799893.2014.917323
Fatima S, et al. Multiple Receptor Conformation Docking, Dock Pose Clustering and 3D QSAR Studies On Human poly(ADP-ribose) Polymerase-1 (PARP-1) Inhibitors. J Recept Signal Transduct Res. 2014;34(5):417-30. PubMed PMID: 25046176.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Multiple receptor conformation docking, dock pose clustering and 3D QSAR studies on human poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors. AU - Fatima,Sabiha, AU - Jatavath,Mohan Babu, AU - Bathini,Raju, AU - Sivan,Sree Kanth, AU - Manga,Vijjulatha, Y1 - 2014/07/21/ PY - 2014/7/22/entrez PY - 2014/7/22/pubmed PY - 2015/5/29/medline KW - Comparative molecular similarity indices analysis KW - multiple receptor conformation docking KW - partial least square analysis KW - poly(ADP-ribose) polymerase-1 KW - three-dimensional quantitative structure activity relationship SP - 417 EP - 30 JF - Journal of receptor and signal transduction research JO - J Recept Signal Transduct Res VL - 34 IS - 5 N2 - Poly(ADP-ribose) polymerase-1 (PARP-1) functions as a DNA damage sensor and signaling molecule. It plays a vital role in the repair of DNA strand breaks induced by radiation and chemotherapeutic drugs; inhibitors of this enzyme have the potential to improve cancer chemotherapy or radiotherapy. Three-dimensional quantitative structure activity relationship (3D QSAR) models were developed using comparative molecular field analysis, comparative molecular similarity indices analysis and docking studies. A set of 88 molecules were docked into the active site of six X-ray crystal structures of poly(ADP-ribose)polymerase-1 (PARP-1), by a procedure called multiple receptor conformation docking (MRCD), in order to improve the 3D QSAR models through the analysis of binding conformations. The docked poses were clustered to obtain the best receptor binding conformation. These dock poses from clustering were used for 3D QSAR analysis. Based on MRCD and QSAR information, some key features have been identified that explain the observed variance in the activity. Two receptor-based QSAR models were generated; these models showed good internal and external statistical reliability that is evident from the [Formula: see text], [Formula: see text] and [Formula: see text]. The identified key features enabled us to design new PARP-1 inhibitors. SN - 1532-4281 UR - https://www.unboundmedicine.com/medline/citation/25046176/Multiple_receptor_conformation_docking_dock_pose_clustering_and_3D_QSAR_studies_on_human_poly_ADP_ribose__polymerase_1__PARP_1__inhibitors_ DB - PRIME DP - Unbound Medicine ER -