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Importance of V3 Loop Flexibility and Net Charge in the Context of Co-Receptor Recognition. A Molecular Dynamics Study on HIV gp120

The entry of HIV-1 into a host cell requires the interaction of envelope glycoprotein gp120 with CD4 receptor as well as a co-receptor, which can be either CCR5 or CXCR4. The third variable loop (V3) of HIV-1 gp120 plays an important role in co-receptor selection (CCR5 or CXCR4) and also acts as an epitope for neutralizing antibodies against gp120. Here we have performed long time molecular dynamics simulations of two gp120 structures that are representatives of a R5 and X4 strains in the CD4-free and CD4-bound states. The results indicate some conserved features in both systems, such as the rigidity of the gp120 core, the conservation of the CD4 Phe43-gp120 binding cavity contacts, a high flexibility of the V3 loop particularly in the CD4 bound form. Analysis of the distribution of V3 loop’s net charge shows it to be more positive for the gp120 sequences selecting CXCR4 co-receptor, letting us to propose that V3 loop net charge and flexibility are the two main elements in the co-receptor selection.

Key words: gp120; CD4-binding; Molecular dynamics; V3 loop.

This article can be cited as:
B. Chandramouli, G. Chillemi, I. Abbate, M.R. Capobianchi, G. Rozera, A. Desideri, Importance of V3 Loop Flexibility and Net Charge in the Context of Co-Receptor Recognition. A Molecular Dynamics Study on HIV gp120 J. Biomol Struct Dyn 29(5), 879-891 (2012).

Balasubramanian Chandramouli1
Giovanni Chillemi2
Isabella Abbate3
Maria R. Capobianchi3
Gabriella Rozera3
Alessandro Desideri1,2*

1Department of Biology, University of Rome Tor Vergata, Via Della Ricerca Scientifica, Rome 00133, Italy
2CASPUR Interuniversities Consortium for Supercomputing Applications, Via dei Tizii 6b, Rome 00185, Italy
3National Institute for Infectious Diseases ‘L. Spallanzani’, Via Portuense 292, Rome, 00149, Italy

*Corresponding author:
Prof. Alessandro Desideri
Phone: 139 06 72594376
Fax: 139 06 2022798
E-mail: desideri@uniroma2.it

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