pH-induced stability switching of the bacteriophage HK97 maturation pathway.
Many viruses undergo large-scale conformational changes during their life cycles. Blocking the transition from one stage of the life cycle to the next is an attractive strategy for the development of antiviral compounds. In this work, we have constructed an icosahedrally symmetric, low-energy pathway for the maturation transition of bacteriophage HK97. By conducting constant-pH molecular dynamics simulations on this pathway, we identify which residues are contributing most significantly to shifting the stability between the states along the pathway under differing pH conditions. We further analyze these data to establish the connection between critical residues and important structural motifs which undergo reorganization during maturation. We go on to show how DNA packaging can induce spontaneous reorganization of the capsid during maturation.
Department of Molecular and Cell Biology, University of Connecticut , Storrs, Connecticut 06269, United States.
Eric R
ER
May
Karunesh
K
Arora
Charles L
CL
Brooks
D002213:Capsid / Q000737:chemistry* / Q000648:ultrastructure; D018360:Crystallography, X-Ray; D006863:Hydrogen-Ion Concentration; D056004:Molecular Dynamics Simulation; D017906:Siphoviridae / Q000254:growth & development* / Q000648:ultrastructure; D013816:Thermodynamics