Molecular dynamics study of structural fluctuations in CDR-H3 of anti-HIV antibodies PG9 and PG16
N. Tanabe1, R. Kiribayashi1, H.X. Kondo2, D. Kuroda3, T. Saito1, J. Kohda1, A. Kugimiya1, Y. Nakano1, K. Tsumoto3,4 and Y. Takano1
1 Graduate School of Information Sciences, Hiroshima City University,
2 Faculty of Engineering, Kitami Institute of Technology.,
3 Institute of Medical science, the University of Tokyo.,
4 Graduate School of Engineering, the University of Tokyo.
Monoclonal antibodies PG9 and PG16 neutralize 70 to 80% of circulating human immunodeficiency virus 1 (HIV-1) isolates. X-ray crystallographic studies of these antibodies have suggested their structural similarity [1]. Both PG9 and PG16 have a 28- residue third complementarity-determining region of the heavy chain (CDR-H3), which forms a unique subdomain referred to as “hammerhead”. In this study we compared the structural fluctuations of the CDR-H3s of these antibodies by using molecular dynamics simulations. Principal component analysis (PCA) of each CDR-H3 revealed that the difference in the structural fluctuation between them. The “hammerhead” tended to bend at the root of CDR-H3 in PG9, while the CDR-H3 of PG16 showed a partial bending of “hammerhead.” The number of hydrogen bonds are associated to these dynamics.
[1] M. Pancera et al., J. Virol. 84, 8098-8110 (2010).