title: Mechanism of polymorphism and curvature of HIV capsid assemblies probed by 3D simulations with a novel coarse grain model.
abstract: BACKGROUND
  During the maturation process, HIV capsid proteins self-assemble into polymorphic capsids. The strong polymorphism precludes high resolution structural characterization under in vivo conditions. In spite of the determination of structural models for various in vitro assemblies of HIV capsid proteins, the assembly mechanism is still not well-understood.
  
  
  METHODS
  We report 3D simulations of HIV capsid proteins by a novel coarse grain model that captures the backbone of the rigid segments in the protein accurately. The effects of protein dynamics on assembly are emulated by a static ensemble of subunits in conformations derived from molecular dynamics simulation.
  
  
  RESULTS
  We show that HIV capsid proteins robustly assemble into hexameric lattices in a range of conditions where trimers of dimeric subunits are the dominant oligomeric intermediates. Variations of hexameric lattice curvatures are observed in simulations with subunits of variable inter-domain orientations mimicking the conformation distribution in solution. Simulations with subunits based on pentameric structural models lead to assembly of sharp curved structures resembling the tips of authentic HIV capsids, along a distinct pathway populated by tetramers and pentamers with the characteristic quasi-equivalency of viral capsids.
  
  
  CONCLUSIONS
  Our results suggest that the polymorphism assembly is triggered by the inter-domain dynamics of HIV capsid proteins in solution. The assembly of highly curved structures arises from proteins in conformation with a highly specific inter-domain orientation.
  
  
  CONCLUSIONS
  Our work proposes a mechanism of HIV capsid assembly based on available structural data, which can be readily verified. Our model can be applied to other large biomolecular assemblies.
authors: Department of Physics, University of Central Florida, 4000 Central Florida Blvd, Orlando, FL 32816, USA.
authors: Xin
authors: X
authors: Qiao
authors: Department of Physics, University of Central Florida, 4000 Central Florida Blvd, Orlando, FL 32816, USA.
authors: Jaekyun
authors: J
authors: Jeon
authors: Department of Physics, University of Central Florida, 4000 Central Florida Blvd, Orlando, FL 32816, USA.
authors: Jeff
authors: J
authors: Weber
authors: Department of Physics, Indiana University - Purdue University Indianapolis, IN, USA.
authors: Fangqiang
authors: F
authors: Zhu
authors: Department of Physics, University of Central Florida, 4000 Central Florida Blvd, Orlando, FL 32816, USA. Electronic address: bo.chen@ucf.edu.
authors: Bo
authors: B
authors: Chen
mesh_terms: D036022:Capsid Proteins / Q000737:chemistry* / Q000235:genetics; D006678:HIV / Q000737:chemistry* / Q000235:genetics; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D011110:Polymorphism, Genetic; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: D036022:Capsid Proteins
keywords: Capsid assembly; Coarse grain simulations; HIV