Abstract
Recently developed reduced models of proteins with knowledge-based force fields have been applied to a specific case of comparative modeling. From twenty high resolution protein structures of various structural classes, significant fragments of their chains have been removed and treated as unknown. The remaining portions of the structures were treated as fixed – i.e., as templates with an exact alignment. Then, the missed fragments were reconstructed using several modeling tools. These included three reduced types of protein models: the lattice SICHO (Side Chain Only) model, the lattice CABS (Cα + Cβ + Side group) model and an off-lattice model similar to the CABS model and called REFINER. The obtained reduced models were compared with more standard comparative modeling tools such as MODELLER and the SWISS-MODEL server. The reduced model results are qualitatively better for the higher resolution lattice models, clearly suggesting that these are now mature, competitive and complementary (in the range of sparse alignments) to the classical tools of comparative modeling. Comparison between the various reduced models strongly suggests that the essential ingredient for the sucessful and accurate modeling of protein structures is not the representation of conformational space (lattice, off-lattice, all-atom) but, rather, the specificity of the force fields used and, perhaps, the sampling techniques employed. These conclusions are encouraging for the future application of the fast reduced models in comparative modeling on a genomic scale.
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References
Baker, D. and Sali, A., Science, 294 (2001) 93.
Chance, M.R., Bresnick, A.R., Burley, S.K., Jiang, J.S., Lima, C.D., Sali, A., Almo, S.C., Bonanno, J.B., Buglino, J.A., Boulton, S., Chen, H., Eswar, N., He, G., Huang, R., Ilyin, V., McMahan, L., Pieper, U., Ray, S., Vidal, M. and Wang, L.K., Protein Sci., 11 (2002) 723.
Montelione, G.T., Zheng, D., Huang, Y.J., Gunsalus, K.C. and Szyperski, T., Nat Struct. Biol., 7 Suppl. (2000) 982.
Simons, K.T., Strauss, C. and Baker, D., J. Mol. Biol., 306 (2001) 1191.
Skolnick, J., Fetrow, J.S. and Kolinski, A., Nature Biotech., 18 (2000) 283.
Pieper, U., Eswar, N., Stuart, A.C., Ilyin, V.A. and Sali, A., Nucleic Acids Res., 30 (2002) 255.
Sali, A., Nat. Struct. Biol., 5 (1998) 1029.
Sali, A. and Blundell, T.L., J. Mol. Biol., 234 (1993) 779.
Fiser, A., Do, R.K. and Sali, A., Protein Sci., 9 (2000) 1753.
Schwede, T., Diemand, A., Guex, N. and Peitsch, M.C., Res. Microbiol., 151 (2000) 107.
Bajorath, J., Stenkamp, R. and Aruffo, A., Protein Sci., 2 (1993) 1798.
van Gunsteren, W.F. and Weiner, P.K., Computer simula-tions of biomolecular systems. Theoretical and experimental applications. 1989, ESCOM Science Publishers B.V.: Leiden.
Kolinski, A. and Skolnick, J., Proteins, 32 (1998) 475.
Kolinski, A., Rotkiewicz, P., Ilkowski, B. and Skolnick, J., Progress of Theoretical Physics (Kyoto), Suppl. 138 (2000) 292.
Kolinski, A., Ilkowski, B. and Skolnick, J., Biophys. J., 77 (1999) 2942.
Skolnick, J., Kolinski, A. and Ortiz, A., Proteins, 38 (2000) 3.
Kolinski, A., Betancourt, M., Kihara, D., Rotkiewicz, P. and Skolnick, J., Proteins, 44 (2001) 133.
Skolnick, J., Kolinski, A., Kihara, D., Betancourt, M., Rotkiewicz, P. and Boniecki, M., Proteins, Suppl. 5 (2001) 149.
Skolnick, J. and Kolinski, A., Adv. Chem. Phys., 1209 (2002) 131.
Kihara, D., Lu, H., Kolinski, A. and Skolnick, J., Proc. Natl. Acad. Sci. USA, 98 (2001) 10125.
Kihara, D., Zhang, Y., Kolinski, A. and Skolnick, J., Proc. Natl. Acad. Sci. USA, 99 (2002) 5993.
Zhang, Y., Kolinski, A. and Skolnick, J., Biophys. J., in press (2003).
Schonbrun, J., Wedemeyer, W.J. and Baker, D., Curr Opin Struct Biol, 12 (2002) 348.
Hukushima, K. and Nemoto, K., J. Phys. Soc. (Jap.), 65 (1996) 1604.
Hansmann, U.H. and Okamoto, Y., Curr. Opin. Struct. Biol., 9 (1999) 177.
Kolinski, A., Jaroszewski, L., Rotkiewicz, P. and Skolnick, J., J. Phys. Chem., 102 (1998) 4628.
Skolnick, J., Zhang, Y., Arakaki, A. K., Kolinski, A., Boniecki, M., Szylagyi, A. and Kihara, D., Proteins (in press)
Feig, M., Rotkiewicz, P., Kolinski, A. and Skolnick, J., Brooks, III, C. L., 41 (2000) 86.
Samudrala, R. and Levitt, M., Protein Sci., 9 (2000) 1399.
Bonneau, R., Ruczinski, I., Tsai, J. and Baker, D., Protein Sci., 11 (2002) 1937.
Yang, A-S. and Wang, L-Y., Bioinformatics 19 (2003) 1267.
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Boniecki, M., Rotkiewicz, P., Skolnick, J. et al. Protein fragment reconstruction using various modeling techniques. J Comput Aided Mol Des 17, 725–738 (2003). https://doi.org/10.1023/B:JCAM.0000017486.83645.a0
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DOI: https://doi.org/10.1023/B:JCAM.0000017486.83645.a0