Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Thinking into Mechanism of Protein Folding and Molecular Binding

Protein folding and molecular binding provide the basis for life on earth. The native 3D structure of a protein is a prerequisite for its function; and the molecular binding is the fundamental principle of all biological processes (1). Therefore unraveling the mechanisms of protein folding and binding is fundamental to describing life at molecular level.

Of particular interest is that protein folding and binding are similar processes because the only difference between them is the presence and absence of the chain connectivity. Among many models (such as diffusion-collision (2), hydrophobic collapse (3) and stoichiometry (4) models) proposed to describe the mechanism of these two processes, the “folding funnel” (5) model (Fig. 1) is most widely accepted. In this model, protein folding can be viewed as going down the free energy hill through multiple parallel pathways towards the bottom of the funnel (6); and molecular binding can occur along rough free energy surface around the funnel bottom, especially for binding between flexible proteins/molecules. These are essentially thermo¬dynamically controlled processes involving various types of driving forces, including the enthalpic contribution of noncovalent bond formations, entropic effects such as solvent release and burial of apolar surface area (hydrophobic effect), restrictions of degrees of freedom of protein/ligand, and loss of rotational and translational freedom of interacting partners. Briefly, these two processes, which are driven by a decrease in total Gibbs free energy (ΔG), are dictated by the mechanism of a delicate balance of the opposing effects of enthalpic (ΔH) and entropic (ΔS) contributions (equation 1).

ΔG =ΔH −TΔS .... ...... ..... .... . [1]

Here we emphasize that it is the thermodynamically driven subtle enthalpy-entropy compensation that leads to the global free energy minimum of the protein/ligand-solvent system (7), and that the specific inter-atomic interactions observed in the folded or complexed structure are to large extent the consequence of thermodynamic equilibrium but can not fully define the driving forces for folding and binding interactions.

Interestingly, we speculate that many other processes can be explained by thermodynamic enthalpy-entropy compensation, i.e., the Yin and Yang balance in traditional Chinese medicine theory could correspond to the enthalpy and entropy compensation of the second law of thermodynamics; global warming can be considered as the consequence of excessive production of positive entropy (carbon dioxide) from chemically ordered fossil fuel, urging people to slow resource consumption to delay the inevitable death by entropy.

A deeper understanding of mechanism of biological processes from thermodynamic point of view can facilitate greatly the understanding of life and rational drug design in the post-genomic times.

Fig. 1 Schematic 2D funnel of protein folding and binding (modified from (6)).

This research was supported by grants from NSFC (No. 30860011) and Yunnan province (2007PY-22), and foundation for Key Teacher of Yunnan University and SRF for ROCS, SEM.


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Xing-Lai Ji1,2
Shu-Qun Liu1,2,*

1Laboratory for Conservation and Utilization of Bio-Resources & Key Laboratory for Microbial Resources of the Ministry of Education, Yunnan University, Kunming 650091, P. R. China
2Sino-Dutch Biomedial and Information Engineering School, Northeastern University, Shenyang 110003, P. R. China

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