Albany 2019: 20th Conversation - Abstracts

Albany 2019
Conversation 20
June 11-15 2019
Adenine Press (2019)

In Silico Assessment of Progesterone Receptor Ligand Binding Domain Using Molecular Dynamic: A new insight into breast cancer treatment

Progesterone receptor (PR), also known as a member of the steroid/nuclear receptor (NR) superfamily, regulates a complex network of distinct target genes. Ligand binding to a PR leads to a conformational change in the receptor, which activates PR to bind to DNA and regulates the transcription (Brennan, M & and B. Lim, 2015). Loss of PR expression is associated with worse overall prognosis and survival among patients with Breast cancer (BC) (Abdel-Hafiz, H. A & K. B. Horwitz, 2012). Although considerable research has been devoted to BC, rather less attention has been paid to PR analysis. In the following research, an extensive in silico analytical study was performed to the computational measurement of PR modulation by a large number of diverse ligands. In this study, we performed molecular dynamic (MD) simulation in two phases. In the first phase, the prepared conformation of PR was used as the initiating structure for MD simulation. The constituents of the simulation system were protein and water. In the 2nd phase, the acquired conformation of PR from the first phase of MD besides the docked ligand was engaged in the MD simulation process. In the docking results, we found a hydrogen-bond between this compound and Arg94 in the PR. Moreover, we docked 12 standard drugs to the PR, which found best docking g score in Levonorgestrel with highest binding energy (-8.35 kcal/mol) and lowest ki (0.758 uM). This drug showed interaction with His31, Asn33, Thr34, Lys35, Pro36, Asp37, Thr38, Ser39, Ser41, Leu42, Asp109, Leu110, Ile111, Leu112, and Arg116 in PR. To show the conformational alignment between best docked natural compound to best docked standard drugs we superimposed these compounds corresponds to PR.

Predicted binding modes of the top-ranked standard drug to the models of PR. (A), A 2-dimensional form conformation of Levonorgestrel docked to PR. (B), A 3-dimensional form conformation of Levonorgestrel docked to PR. In 3-D format, PR is green and magenta color, while for ligands (Levonorgestrel), carbon atoms are cyan; oxygen atoms are red and nitrogen atoms are blue.

    Brennan, M., and B. Lim. "The Actual Role of Receptors as Cancer Markers, Biochemical and Clinical Aspects: Receptors in Breast Cancer." Adv Exp Med Biol 867, 327-337 (2015). DOI: 10.1007/978-94-017-7215-0_20

    Abdel-Hafiz, H. A., and K. B. Horwitz. "Control of Progesterone Receptor Transcriptional Synergy by Sumoylation and Desumoylation." BMC Mol Biol 13 (Mar 22 2012): Article No. 10. DOI: 10.1186/1471-2199-13-10

Vahid Zarezade1
Marzie Abolghasemi1
Fakher Rahim2, 3
Ali Veisi1

1 Behbahan University of Medical Sciences, Iran.
2Health Research Institute, Thalassemia and Hemoglobinopathies Research Centre, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
3Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.

Email: = bioinfo2003@gmail.com