Computational Exploration for Lead Compounds That Can Reverse the Nuclear Morphology in Progeria

Joint Authors

Rampogu, Shailima
Son, Minky
Park, Chanin
Lee, Keun Woo
Baek, Ayoung
Zeb, Amir
Kumar, Raj
Lee, Gihwan
Kim, Donghwan
Choi, Yeonuk
Cho, Yeongrae
Park, Yohan
Park, Seok Ju

Source

BioMed Research International

Issue

Vol. 2017, Issue 2017 (31 Dec. 2017), pp.1-15, 15 p.

Publisher

Hindawi Publishing Corporation

Publication Date

2017-10-26

Country of Publication

Egypt

No. of Pages

15

Main Subjects

Medicine

Abstract EN

Progeria is a rare genetic disorder characterized by premature aging that eventually leads to death and is noticed globally.

Despite alarming conditions, this disease lacks effective medications; however, the farnesyltransferase inhibitors (FTIs) are a hope in the dark.

Therefore, the objective of the present article is to identify new compounds from the databases employing pharmacophore based virtual screening.

Utilizing nine training set compounds along with lonafarnib, a common feature pharmacophore was constructed consisting of four features.

The validated Hypo1 was subsequently allowed to screen Maybridge, Chembridge, and Asinex databases to retrieve the novel lead candidates, which were then subjected to Lipinski’s rule of 5 and ADMET for drug-like assessment.

The obtained 3,372 compounds were forwarded to docking simulations and were manually examined for the key interactions with the crucial residues.

Two compounds that have demonstrated a higher dock score than the reference compounds and showed interactions with the crucial residues were subjected to MD simulations and binding free energy calculations to assess the stability of docked conformation and to investigate the binding interactions in detail.

Furthermore, this study suggests that the Hits may be more effective against progeria and further the DFT studies were executed to understand their orbital energies.

American Psychological Association (APA)

Rampogu, Shailima& Baek, Ayoung& Son, Minky& Zeb, Amir& Park, Chanin& Kumar, Raj…[et al.]. 2017. Computational Exploration for Lead Compounds That Can Reverse the Nuclear Morphology in Progeria. BioMed Research International،Vol. 2017, no. 2017, pp.1-15.
https://search.emarefa.net/detail/BIM-1137519

Modern Language Association (MLA)

Rampogu, Shailima…[et al.]. Computational Exploration for Lead Compounds That Can Reverse the Nuclear Morphology in Progeria. BioMed Research International No. 2017 (2017), pp.1-15.
https://search.emarefa.net/detail/BIM-1137519

American Medical Association (AMA)

Rampogu, Shailima& Baek, Ayoung& Son, Minky& Zeb, Amir& Park, Chanin& Kumar, Raj…[et al.]. Computational Exploration for Lead Compounds That Can Reverse the Nuclear Morphology in Progeria. BioMed Research International. 2017. Vol. 2017, no. 2017, pp.1-15.
https://search.emarefa.net/detail/BIM-1137519

Data Type

Journal Articles

Language

English

Notes

Includes bibliographical references

Record ID

BIM-1137519