pH-induced stability switching of the bacteriophage HK97 maturation pathway

J Am Chem Soc. 2014 Feb 26;136(8):3097-107. doi: 10.1021/ja410860n. Epub 2014 Feb 13.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Capsid / chemistry*
  • Capsid / ultrastructure
  • Crystallography, X-Ray
  • Hydrogen-Ion Concentration
  • Molecular Dynamics Simulation
  • Siphoviridae / growth & development*
  • Siphoviridae / ultrastructure
  • Thermodynamics