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Original Research Article
Molecular Dynamics and
Bioactivity of a Novel Mutated Human Parathyroid Hormone
Yueshui Jiang1,
Jiande Gu2, Jianyong Lei1, Yun
Chen1 and Jian Jin1,3*
1School of Pharmaceutical
Sciences, Jiangnan University, 1800 Lihu Road, Wuxi,
Jiangsu 214122, 2Drug Design & Discovery
Center, Shanghai Institute of Materia Medica, Shanghai
Institutes for Biological Sciences, Chinese Academy of
Sciences, Shanghai 201203, 3Institute of
Health Sciences, Shanghai Institutes for Biological
Sciences, Chinese Academy of Sciences & Shanghai
Jiao-Tong University School of Medicine, 320 Yue-Yang
Road, Shanghai 200031, PR China
*For correspondence:
Email:
jinjian31@126.com; Tel/Fax: +86
510 8591 8219
Received: 3 May 2013
Revised accepted: 28
February 2014
Tropical
Journal of Pharmaceutical Research, April 2014;
13(4):
511-518
http://dx.doi.org/10.4314/tjpr.v13i4.4
Abstract
Purpose: To design and evaluate a
novel human parathyroid hormone (hPTH) analog.
Methods: Mutation stability
prediction was processed on hPTH, docked the mutant hPTH
with its receptor, and then proceeded with molecular
dynamics using Discovery Studio 3.5 software package for
the complex. The bioactivity of the hPTH on the
expression levels of the Rps27, RANKL and OPG genes were
assessed in UAMS-32P cells.
Results: A three-site mutant, hPTH
(R25Q:K26E:K27L), was obtained and MD trajectory
analysis showed a decrease in the root mean square
deviation by 51.95%, in the radius of gyration by 3.57%,
and in the interaction energy by 10%, compared with the
wild-type hPTH. Bioactivity assessment demonstrated that
this mutant stimulated the ratio of RANKL/OPG 30-fold
higher than the wild-type.
Conclusion: We successfully designed a
new hPTH mutant with a stable conformation and high
bioactivity, and this may be useful for elucidating
ligand-receptor recognition mechanism and discovering
novel hPTH analogs.
Keywords: Parathyroid hormone,
Mutation prediction, Molecular dynamics, RANKL/OPG,
UAMS-32P cell |
