A molecular dynamics study of loop fluctuation in human papillomavirus type 16 virus-like particles: a possible indicator of immunogenicity.
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.
Chemistry Department, Indiana University, Bloomington, IN 47405, USA.
Harshad
H
Joshi
Srinath
S
Cheluvaraja
Endre
E
Somogyi
Darron R
DR
Brown
Peter
P
Ortoleva
D000914:Antibodies, Viral / Q000276:immunology; D002213:Capsid / Q000276:immunology; D036022:Capsid Proteins / Q000737:chemistry* / Q000276:immunology*; D000939:Epitopes; D005260:Female; D052162:Human papillomavirus 16 / Q000276:immunology*; D006801:Humans; D008958:Models, Molecular; D056004:Molecular Dynamics Simulation; D009500:Neutralization Tests; D009856:Oncogene Proteins, Viral / Q000737:chemistry* / Q000276:immunology*; D053918:Papillomavirus Vaccines; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D002583:Uterine Cervical Neoplasms / Q000517:prevention & control
D000914:Antibodies, Viral; D036022:Capsid Proteins; D000939:Epitopes; D009856:Oncogene Proteins, Viral; D053918:Papillomavirus Vaccines; C063317:L1 protein, Human papillomavirus type 16