Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Molecular Dynamics and Bioactivity of a Novel Mutated Human Parathyroid Hormone

Yueshui Jiang¹, Jiande Gu², Jianyong Lei¹, Yun Chen¹, Jian Jin^1,3

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:- Jian Jin Email: jinjian31@126.com Tel:+8651085918219

Received: 3 May 2013 Accepted: 28 February 2014 Published: 23 April 2014

Citation: Jiang Y, Gu J, Lei J, Chen Y, Jin J. Molecular Dynamics and Bioactivity of a Novel Mutated Human Parathyroid Hormone. Trop J Pharm Res 2014; 13(4):511-518 doi: 10.4314/tjpr.v13i4.4

© 2014 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

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