Suggested binding mechanism of the HIV-gp120 to its CD4 receptor

Zoltán Székely, Zoltán Kónya, Attila Becskei, W. P. D. Goldring, András Perczel, Botond Penke, József Molnár, Christopher F. Michejda, Adorján Aszalós, Imre G. Csizmadia

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Abstract

The molecular recognition and attachment of the CD4 molecule and the HIV envelope glycoprotein (gp120) might be described as a consecutive three-step molecular recognition process.

1. (a) Long range interaction: electrostatic pre-orientation,
2. (b) short range interaction: electronic attachment followed by a ‘Locking-in’ (via aromatic ring orientation) and
3. (c) internal interaction (induced fit): conformational readjustment of the protein molecules.

On the basis of the preliminary investigations (X-ray structures of CD4 and biological studies of CD4 and gp120 point mutants) we described a computational model. This approach consists of empirical calculations as well as ab initio level of quantum chemistry. The conformational analysis of the wild type and mutant CD4 molecules was supported by molecular mechanics and dynamics (Amber force field). The latter analysis involves the application of a novel method, the Amino Acid Conformation Assignment of Proteins (ACAP) software, developed for the notation of secondary protein structures. According to the cardinal role of the electrostatic factors during this interaction, several ab initio investigations were performed for better understanding of the recognition process on submolecular level. Using the above mentioned computational model, we could interpret the basic behaviours and predict some additional features of CD4-gp120 interaction, in spite of the missing gp120 X-ray structure.
OriginalsprogEngelsk
TidsskriftJournal of Molecular Structure: THEOCHEM
Vol/bind367
Sider (fra-til)159-186
Antal sider28
ISSN0166-1280
DOI
StatusUdgivet - 1996
Udgivet eksterntJa

Citer dette

Székely, Z., Kónya, Z., Becskei, A., Goldring, W. P. D., Perczel, A., Penke, B., Molnár, J., Michejda, C. F., Aszalós, A., & Csizmadia, I. G. (1996). Suggested binding mechanism of the HIV-gp120 to its CD4 receptor. Journal of Molecular Structure: THEOCHEM, 367, 159-186. https://doi.org/10.1016/S0166-1280(96)04501-0