title: Structure and dynamics of the monomer  of protein E of dengue virus type 2 with unprotonated histidine residues.
abstract: The surface of the dengue virus is composed of 180  copies of a multifunctional envelope glycoprotein that acts at several stages  of viral infection. When the virus is in the endosome, these glycoproteins  undergo major conformational rearrangements owing to the protonation of  histidine side chains. This protonation allows for the formation of trimers,  thereby triggering fusion between the viral and the host membranes. In this  study, we examined the behavior of a monomer of this key protein containing  unprotonated histidine side chains before the stage of trimer formation using  explicit solvent molecular dynamics at various ionic strengths. The extended  secondary structures, which contribute to protein stabilization, are smaller  than those observed in a previous study involving monomers containing the  protonated histidine. However, the structure of the monomer investigated herein  is extremely stable under ionic strengths ranging from 0 to 225 mM. The results  show that a protein surface frozen owing to interactions between charged groups  is mainly responsible for this stabilization. Thus, focusing on binding sites  and ligands that destabilize these properties can aid the search for dengue  virus inhibitors.
authors: Grupo de Simulação Molecular, Departamento de Química, Faculdade de Filosofia Ciências e Letras de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brasil. leo@fcfrp.usp.br
authors: L
authors: L
authors: Degrève
authors: C A
authors: CA
authors: Fuzo
mesh_terms: D001665:Binding Sites; D003716:Dengue Virus / Q000378:metabolism*; D006639:Histidine / Q000737:chemistry* / Q000378:metabolism*; D006860:Hydrogen Bonding; D008024:Ligands; D056004:Molecular Dynamics Simulation; D017433:Protein Structure, Secondary; D014759:Viral Envelope Proteins / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D008024:Ligands; D014759:Viral Envelope Proteins; D006639:Histidine