computer modeling in molecular biology.pdf

7 Major Histocompatibility Complex Class I Protein-Peptide Interactions 21 1answers which are extremely similar to those obtained by X-ray crystallography. Dueto the vast difference in time scale between performing a modelling exercise andcrystallising a complex of an MHC class I molecule and its peptide partner, for caseswhere a qualitive answer to questions of the function and position of residues in theMHC class I molecule or the peptide for mutagenesis studies is required, the modelsproduced using the techniques described here are more than adequate. Where aquantitative answer is required, as in all modelling exercises and simulations, onlydirect structural analysis will provide an unequivocal solution. In the case of manyMHC class I peptide studies this unequivocal answer is highly similar in its conclusionsto those drawn from the model.AcknowledgementsThe contributions of Alan Rickenson, Andreas Ziegler, Jonathan Howard, AlanLamont, Neera Borkakoti, Julia Goodfellow and especially Paul Travers to this workare gratefully acknowledged. In addition the contributions of Tom Blundell andmembers of the ICRF Unit for Structural Molecular Biology to interesting andstimulating discussions are acknowledged. CJT is the recipient of an SERC CASEaward in collaboration with Roche Products U.K. CJT and DSM acknowledge thecontinuing support of Tripos Associates.References[l] Townsend, A., Bodmer, H., Annu. Rev. Immunof. 1989, 7, 601-624.[2] Gorer, P. A., J Pathol. Bacteriol. 1937, 44, 691.[3] Klein, J., Natural history of the major histocompatibility complex. J. Wiley & Sons Inc.,New York, 1986.[4] Brown, J. H., Jardetzky, T, S., Gorga, J. C., Stern, L. J., Urban, R. G., Strominger, J. L.,Wiley, D. C., Nature 1993, 364, 33-39.[5] Madden, D. R., Gorga, J. C., Strominger, J. L., Wiley, D. C., Cell 70, 1992, 1035-1048.[6] Thorpe, C. J., Immunology Today 1993, 14, 51-52.[7] Travers, P. J., Thorpe, C. J., Curr. Biol. 1992, 2, 679-681.[8] Elliot, T., Smith, M., Driscoll, P., McMichael, A., Curr. Biol. 1993, 3, 854-866.[9] Trowsdale, J., Hanson, I., Mockridge, I., Beck, S., Townsend, A., Kelly, A., Nature 1990,348, 741 -744.[lo] Robson MacDonald, H., Curr. Biol. 1992, 2, 653-655.[Ill Falk, K. Rotzschke, O., Setvanovich, S., Jung, G., Rammensee, H.-G., Nature 1991, 351,290-296.[12] Jardetzky, T. H., Lane, W. S., Robinson, R. A., Madden, D. R., Wiley, D. C., Nature1991, 353, 326-329.