Studies on binding free energies and the binding mode by docking and MM-PBSA in gp41-ligand complex

Abstract

Despite the synthetic peptides inhibit HIV-1 entry, its application may be limited due to the high cost of the peptide production and lack of its oral availability. Thus, it is necessary to identify the small molecule inhibitors reacting with the same or overlapping target sites on gp41 recognizing the antiviral peptides. In this paper, a small inhibitor (TP1) is docked into the hydrophobic grooves of gp41 by using Autodock software, resulting in five alternative energetically favorable models. The molecular mechanics-Poisson Boltzmann surface area (MM-PBSA) method is applied to calculate the binding free energies. The data from other studies were used to define our preferred models. We found that only one binding mode is supported by the experimental evidence. The model could be used to design more effective HIV-1 inhibitors targeted to the HIV-1 gp41 core structure.

Keywords:

• MM-PBSA
• Binding free energies
• Binding mode
• Gp41

Acknowledgements

The authors thank Beijing Natural Science Foundation (No. 5032002 and 5042003) and the Fund from Beijing City Education Committee (No. KZ200410005002) for financial supports.

Notes

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Additional information

Notes on contributors

J. J. TAN

¶ ¶[email protected].: [phone]. Fax: [phone]

R. KONG

‡ ‡[email protected].: [phone]. Fax: [phone]

C. X. WANG

† †[email protected].: [phone]. Fax: [phone]