Interdisciplinary Sciences: Computational Life Sciences

, Volume 1, Issue 3, pp 214–219

Structural flexibility and interactions of PTP1B’s S-loop

Article

DOI: 10.1007/s12539-009-0047-4

Cite this article as:
Wang, JF., Gong, K., Wei, DQ. et al. Interdiscip Sci Comput Life Sci (2009) 1: 214. doi:10.1007/s12539-009-0047-4

Abstract

Protein-tyrosine phosphatase 1B (PTP1B) is an attractive drug target for type II diabetes and obesity. The structural motions of its S-loop play crucial roles in WPD-loop closure that is essential for the catalytic mechanism of this protein. In the current studies, totally 20 ns molecular dynamics simulations were employed on both PTP1B and its complex with inhibitors in the explicit solution surroundings with the periodic boundary conditions in order to perform detail exam on the structural flexibility of S-loop. Together with calculating RMSD values and monitoring the distances between active site and the residues in S-loop, it is found that S-loop can move towards to active site and form a tight binding pocket for substrates upon inhibitor binding. And a hydrogen bond network rearrangement was detected in this region, which may cause the transforms of both the tree-dimensional structure and the total accessible surfaces for the residues in S loop. Additionally, the second structures of Ser201 and Gly209 have huge changes for the open system, which is not detected in close system. These findings can reveal the possible mechanism of ligand recognitions and inhibitions, further providing useful information to design novel inhibitors against PTP1B and develop new treatment for type II diabetes and obesity.

Key words

protein-tyrosine phosphatase 1Btype II diabetes and obesitymolecular dynamics simulationsessential dynamics analysisS-loop flexibility

Copyright information

© International Association of Scientists in the Interdisciplinary Areas and Springer-Verlag GmbH 2009

Authors and Affiliations

  1. 1.Bioinformatics Center, Key Laboratory of Systems Biology, Shanghai Institutes for Biological SciencesChinese Academy of SciencesShanghaiChina
  2. 2.Department of Bioinformatics and Biostatistics, School of Life Science and BiotechnologyShanghai Jiao Tong UniversityShanghaiChina