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Molecular docking of superantigens with class II major histocompatibility complex proteins
Author(s) -
Olson Mark A.,
Cuff Lilee
Publication year - 1997
Publication title -
journal of molecular recognition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.401
H-Index - 79
eISSN - 1099-1352
pISSN - 0952-3499
DOI - 10.1002/(sici)1099-1352(199711/12)10:6<277::aid-jmr376>3.0.co;2-x
Subject(s) - superantigen , major histocompatibility complex , computational biology , docking (animal) , histocompatibility , biology , chemistry , immunology , antigen , human leukocyte antigen , immune system , medicine , t cell , nursing
The molecular recognition of two superantigens with class II major histocompatibility complex molecules was simulated by using protein– protein docking. Superantigens studied were staphylococcal enterotoxin B (SEB) and toxic shock syndrome toxin‐1 (TSST‐1) in their crystallographic assemblies with HLA‐DR1. Rigid‐body docking was performed sampling configurational space of the interfacial surfaces by employing a strategy of partitioning the contact regions on HLA‐DR1 into separate molecular recognition units. Scoring of docked conformations was based on an electrostatic continuum model evaluated with the finite‐difference Poisson– Boltzmann method. Estimates of nonpolar contributions were derived from the buried molecular surface areas. We found for both superantigens that docking the HLA‐DR1 surface complementary with the SEB and TSST‐1 contact regions containing a homologous hydrophobic surface loop provided sufficient recognition for the reconstitution of native‐like conformers exhibiting the highest‐scoring free energies. For the SEB complex, the calculations were successful in reproducing the total association free energy. A comparison of the free‐energy determinants of the conserved hydrophobic contact residue indicates functional similarity between the two proteins for this interface. Though both superantigens share a common global association mode, differences in binding topology distinguish the conformational specificities underlying recognition. © 1998 John Wiley & Sons, Ltd.