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BioMed Research International
Volume 2017 (2017), Article ID 5270940, 15 pages
Research Article

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

1Division of Applied Life Science (BK21 Plus), Plant Molecular Biology and Biotechnology Research Center (PMBBRC), Systems and Synthetic Agrobiotech Center (SSAC), Research Institute of Natural Science (RINS), Gyeongsang National University (GNU), 501 Jinju-daero, Jinju 52828, Republic of Korea
2College of Pharmacy, Inje University, 197 Inje-ro, Gimhae, Gyeongnam 50834, Republic of Korea
3Department of Internal Medicine, College of Medicine, Busan Paik Hospital, Inje University, Gyeongnam, Republic of Korea

Correspondence should be addressed to Seok Ju Park and Keun Woo Lee

Received 25 July 2017; Accepted 24 September 2017; Published 26 October 2017

Academic Editor: Rituraj Purohit

Copyright © 2017 Shailima Rampogu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.