Journal of Molecular Modeling

, Volume 13, Issue 3, pp 411–424

Dynamic domains and geometrical properties of HIV-1 gp120 during conformational changes induced by CD4 binding

Original Paper

DOI: 10.1007/s00894-006-0158-3

Cite this article as:
Liu, SQ., Liu, SX. & Fu, YX. J Mol Model (2007) 13: 411. doi:10.1007/s00894-006-0158-3

Abstract

The HIV-1 gp120 exterior envelope glycoprotein undergoes a series of conformational rearrangements while sequentially interacting with the receptor CD4 and coreceptor CCR5 or CXCR4 on the surface of host cells to initiate virus entry. Both the crystal structures of the HIV-1 gp120 core bound by the CD4 and antigen 17b, and the SIV gp120 core pre-bound by the CD4 are known. We have performed dynamic domain studies on the homology models of the CD4-bound and unliganded HIV-1 gp120 with modeled V3 and V4 loops to explore details of conformational changes, hinge axes, and hinge bending regions in the gp120 structures upon CD4 binding. Four dynamic domains were clustered and intricately motional modes for domain pairs were discovered. Together with the detailed comparative analyses of geometrical properties between the unliganded and liganded gp120 models, an induced fit model was proposed to explain events accompanying the CD4 engagement to the gp120, which provided new insight into the dynamics of the molecular induced binding mechanism that complements the molecular dynamics and crystallographic studies.

Keywords

HIV-1 gp120 CD4 Dynamic domain Geometrical property Interaction Induced fit 

Abbreviations

HIV

human immunodeficiency virus

SIV

simian immunodeficiency virus

AIDS

acquired immunodeficiency syndrome

MD

molecular dynamics

Fab

antigen binding fragment

V

variable loop

PND

principle neutralizing determinant

NMR

nuclear magnetic resonance

RMSD

root mean square deviation

CD4-BL

CD4-binding-loop

Rg

radiuses of gyration

SASA

solvent accessible surface area

NNC

number of native contacts

NHB

number of hydrogen bonds

SSE

secondary structure element

CD4BS

CD4-binding site

CD4I

CD4-induced

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  1. 1.Laboratory for Conservation and Utilization of Bio-resourcesYunnan UniversityKunmingPeople’s Republic of China
  2. 2.School of Chemical Science and TechnologyYunnan UniversityKunmingPeople’s Republic of China
  3. 3.Human Genetics CenterThe University of Texas Health Science CenterHoustonUSA

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