第3讲免疫系统仿真.pptVIP

MHC-peptide complexes: Results The loop regions have large deviations from the x-ray structure, while the two long helices and the b-sheets have relatively small deviations. RMS deviations of peptide (top) and antigen-binding site of MHC protein (bottom) from x-ray structure. Solid line: whole system simulation; Dashed line: partial system simulation. MHC-peptide complexes: Conclusions For 58,825 atoms system, 1 ns simulation can be performed in 17 hours wall clock time on 256 processors of T3E. More accurate results are obtained by simulating the whole complex than just a part of it. The a3 and b2m domains have a significant influence on the structural and dynamical features of the complex, which is very important for determining the binding efficiencies of epitopes. We are now doing TCR-peptide-MHC simulations (~ 100,000 atom model) using NAMD. Cyclical refinement refine Initial experiments Optimise/ clean Computer models define Further experiments Other work Identification of relationship between TAP transporter and MHC binding using KDD techniques Brusic et al. (1999). In Silico Biology 1, 109-121. Daniel et al. (1998). Journal of Immunology 161, 617-624. Prediction of cancer-related T-cell epitopes Zarour et al. (2002). Canc. Res. 62, 213-218. Kierstad et al. (2001). Br. J. Canc. 85, 1735-1745. Zarour et al. (2000). Canc. Res. 60, 4946-4952. Zarour et al. (2000). PNAS USA 97, 400-405. Prediction of peptides that bind multiple MHC molecules Brusic et al. (2002). Immunology and Cell Biology 80, 280-285. Large-scale (genome-wide) screening of MHC binders Sch?nbach et al. (2002). Immunology and Cell Biology 80, 300-306. Prediction of renal transplant outcomes Petrovsky et al (2002). Graft 4, 6-13. A substantial effort is required to model a single MHC molecule There are more than 1000 different human MHC molecules and growing The number of pathogen genomes for vaccine design is increasing rapidly Thus vaccine target identification is a