The current view of protein structure now includes a realization that proteins continually undergo complex and hierarchical conformational changes while carrying out their biological functions, e.g., in signal transduction, immune response, protein folding, and enzymatic activity. Large-scale conformational changes of proteins are usually associated with the binding of ligands. Because the conformational changes are often related to the biological functions of proteins, understanding the molecular mechanisms of these motions and the effects of ligand binding becomes very necessary.

The protein conformational transition coupled with the biological function has attracted much attention in the last several decades. Various methods in both experiments and theoretical simulations have been utilized to understand the molecular mechanism of protein conformational transition. However, the difficulty in capturing the transition pathway makes the mechanism unclear yet.  

To make a systemic study of the molecular mechanism of protein conformational change and the effects from ligand binding, in the present study, The research group led by Prof. ZHU Weiliang in Shanghai Institute of Materia Medica, CAS combine a normal-mode analysis (NMA) method in internal coordinates (iMOD) and umbrella sampling MD simulation to investigate three typical protein systems: the phosphotransferase enzyme adenylate kinase (AdK) from Escherichia coli, the Ca²⁺-binding protein calmodulin (CaM), and the p38a mitogen-activated protein kinase (MAPK).

These observations indicate the mechanism diversity of protein conformational change, suggesting that the detailed mechanism of ligand binding and the associated conformational transition is not uniform for all kinds of proteins but may be correlated to their structural flexibility and respective biological functions. 

This research work was performed by Dr. Wang Jin’an. The study has been published in the Journal of Physical Chemistry B.

Full text: http://pubs.acs.org/doi/ipdf/10.1021/jp4105129