title: In silico grouping of peptide/HLA class I complexes using structural interaction characteristics.
abstract: BACKGROUND
  Classification of human leukocyte antigen (HLA) proteins into supertypes underpins the development of epitope-based vaccines with wide population coverage. Current methods for HLA supertype definition, based on common structural features of HLA proteins and/or their functional binding specificities, leave structural interaction characteristics among different HLA supertypes with antigenic peptides unexplored.
  
  
  METHODS
  We describe the use of structural interaction descriptors for the analysis of 68 peptide/HLA class I crystallographic structures. Interaction parameters computed include the number of intermolecular hydrogen bonds between each HLA protein and its corresponding bound peptide, solvent accessibility, gap volume and gap index.
  
  
  RESULTS
  The structural interactions patterns of peptide/HLA class I complexes investigated herein vary among individual alleles and may be grouped in a supertype dependent manner. Using the proposed methodology, eight HLA class I supertypes were defined based on existing experimental crystallographic structures which largely overlaps (77% consensus) with the definitions by binding motifs. This mode of classification, which considers conformational information of both peptide and HLA proteins, provides an alternative to the characterization of supertypes using either peptide or HLA protein information alone.
authors.affiliation: Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore 8 Medical Drive, Singapore 117597.
authors.forename: Joo Chuan
authors.initials: JC
authors.lastname: Tong
authors.forename: Tin Wee
authors.initials: TW
authors.lastname: Tan
authors.forename: Shoba
authors.initials: S
authors.lastname: Ranganathan
mesh_terms: D000483:Alleles; D001185:Artificial Intelligence; D001665:Binding Sites; D003198:Computer Simulation; D018604:Epitope Mapping / Q000379:methods*; D015395:Histocompatibility Antigens Class I / Q000737:chemistry* / Q000145:classification* / Q000276:immunology; D008956:Models, Chemical; D018448:Models, Immunological; D005810:Multigene Family / Q000276:immunology*; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D016415:Sequence Alignment / Q000379:methods; D020539:Sequence Analysis, Protein / Q000379:methods*; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship
chemical_list: D015395:Histocompatibility Antigens Class I