A molecular dynamics study of loop fluctuation in human papillomavirus type 16 virus-like particles: a possible indicator of immunogenicity

Vaccine. 2011 Nov 28;29(51):9423-30. doi: 10.1016/j.vaccine.2011.10.039. Epub 2011 Oct 24.

Abstract

Immunogenicity varies between the human papillomavirus (HPV) L1 monomer assemblies of various sizes (e.g., monomers, pentamers or whole capsids). The hypothesis that this can be attributed to the intensity of fluctuations of important loops containing neutralizing epitopes for the various assemblies is proposed for HPV L1 assemblies. Molecular dynamics simulations were utilized to begin testing this hypothesis. Fluctuations of loops that contain critical neutralizing epitopes (especially FG loop) were quantified via root-mean-square fluctuation and features in the frequency spectrum of dynamic changes in loop conformation. If this fluctuation-immunogenicity hypothesis is a universal aspect of immunogenicity (i.e., immune system recognition of an epitope within a loop is more reliable when it is presented via a more stable delivery structure), then fluctuation measures can serve as one predictor of immunogenicity as part of a computer-aided vaccine design strategy.

Publication types

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

MeSH terms

  • Antibodies, Viral / immunology
  • Capsid / immunology
  • Capsid Proteins / chemistry*
  • Capsid Proteins / immunology*
  • Epitopes
  • Female
  • Human papillomavirus 16 / immunology*
  • Humans
  • Models, Molecular
  • Molecular Dynamics Simulation*
  • Neutralization Tests
  • Oncogene Proteins, Viral / chemistry*
  • Oncogene Proteins, Viral / immunology*
  • Papillomavirus Vaccines
  • Protein Conformation
  • Protein Structure, Tertiary
  • Uterine Cervical Neoplasms / prevention & control

Substances

  • Antibodies, Viral
  • Capsid Proteins
  • Epitopes
  • Oncogene Proteins, Viral
  • Papillomavirus Vaccines
  • L1 protein, Human papillomavirus type 16