Abstract
A number of challenging computational problems arise in the field of structure-based drug design, including the estimation of ligand binding affinity and the de novo design of novel ligands. An important step toward solutions of these problems is the consistent and rapid prediction of the thermodynamically most favorable structure of a ligand—protein complex from the three-dimensional structures of its unbound ligand and protein components. This fundamental problem in molecular recognition is commonly known as the docking problem [1–3]. To solve this problem, two distinct conditions must be satisfied. The first is a thermodynamic requirement: the energy function used to describe ligand—protein binding must have the crystal structure of ligand—protein complexes as its global energy minimum. The second is a kinetic requirement: it must be possible to locate consistently and rapidly the global energy minimum on the ligand—protein binding energy landscape. While the first condition is necessary for successful structure prediction, it is by no means sufficient. Without kinetic accessibility, the global minimum cannot be reached during docking simulations, and computational structure prediction will fail. Here we review approaches to address both the kinetic and thermodynamic aspects of the docking problem.
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References
Wodak, S.J. and Janin, J., J. Mol. Biol., 124(1978)323.
Kuntz, I.D., Blaney, J.M., Oatley, S.J., Langridge, R. and Ferrin, T.E., J. Mol. Biol., 161(1982)269.
Cherfils, J. and Janin, J., Curr. Opin. Struct. Biol., 3(1993)265.
Shoichet, B.K. and Kuntz, I.D., J. Mol. Biol., 221(1991)327.
Wang, H.J., J. Comput. Chem., 12(1991)746.
Jiang, F. and Kim, S.H., J. Mol. Biol., 219(1991)79.
Desjarlais, R.L., Sheridan, R.P., Dixon, J.S., Kuntz, I.D. and Venkataraghavan, R., J. Med. Chem., 29 (1986) 2149.
Desjarlais, R.L. and Dixon, J.S., J. Comput.-Aided Mol. Design, 8(1994)231.
Shoichet, B.K. and Kuntz, I.D., Protein Eng., 6(1993)723.
Walls, P.H. and Sternberg, M.J.E., J. Mol. Biol., 228(1992)277.
Jackson, R.M. and Sternberg, M.J.E., J. Mol. Biol., 250(1995)258.
Stoddard, B.L. and Koshland, D.E., Proc. Natl. Acad. Sci. USA, 90 (1993) 1146.
Katchalski-Katzir, E., Shariv, I., Eisenstein, M., Friesem, A.A., Aflalo, C. and Vakser, I.A., Proc. Natl. Acad. Sci. USA, 89 (1992) 2195.
Fisher, D., Lin, S.L., Wolfson, H.J. and Nussinov, R., J. Mol. Biol., 248(1995)459.
Vakser, I.A. and Aflalo, C., Proteins Struct. Funct. Genet., 20(1994)320.
Goodsell, D.S. and Olson, A.J., Proteins Struct. Funct. Genet., 8(1990)195.
Yue, S.Y., Proteins, 4 (1990) 177.
Caflisch, A., Niederer, P. and Anliker, M., Proteins Struct. Funct. Genet., 13(1992)223.
Hart, T.N. and Read, R.J., Proteins Struct. Funct. Genet., 13(1992)206.
Totrov, M. and Abagyan, R., Nat. Struct. Biol., 1(1994)259.
DiNola, A., Roccatano, D. and Berendsen, H.J.C., Proteins Struct. Funct. Genet., 19(1994)174.
Zacharias, M., Luty, B.A., Davis, M.E. and McCammon, J.A., J. Mol. Biol., 238 (1994)455.
Leach, A.R., J. Mol. Biol., 235(1994)345.
Kuhl, F.S., Crippen, G.M. and Friesen, D.K., J. Comput. Chem., 5(1984)24.P.A. Repo et al.
Levinthal, C., In DeBrunner, P., Tsibris, J. and Munck, E. (Eds.) Mossbauer Spectroscopy in Biological Systems, Proceedings of a meeting held at Allerton House, Monticello, Urbana, IL, University of Illinois Press, Champaign, IL, 1969, pp. 22–24.
Bryngelson, J.D. and Wolynes, P.G., Proc. Natl. Acad. Sci. USA, 84(1987)7524.
Goldstein, R.A., Luthey-Schulten, Z.A. and Wolynes, P.G., Proc. Natl. Acad. Sci. USA, 89(1992)9029.
Shakhnovich, E.I. and Gutin, A.M., Proc. Natl. Acad. Sci. USA, 90(1993)7195.
Sali, A., Shakhnovich, E.I. and Karplus, M., J. Mol. Biol., 235 (1994) 1614.
Chan, H.S. and Dill, K.A., J. Chem. Phys., 100(1994)9238.
Leopold, P.E., Montai, M. and Onuchic, J.N., Proc. Natl. Acad. Sci. USA, 89(1992)8721.
Socci, N.D. and Onuchic, J.N., J. Chem. Phys., 101 (1994) 1519.
Bryngelson, J.D., Onuchic, J.N., Socci, N.D. and Wolynes, P.G., Proteins Struct. Funct. Genet., 21(1995)167.
Dill, K.A., Bromberg, S., Yue, K., Fiebig, K.M., Yee, D.P., Thomas, P.D. and Chan, H.S., Protein Sci., 4(1995)561.
Goldberg, D.E., Genetic Algorithms in Search, Optimization and Machine Learning, Addison-Wesley, Reading, MA, 1989.
Xiao, Y.L. and Williams, D.E., J. Phys. Chem., 98(1994)7191.
Oshiro, C.M., Kuntz, I.D. and Dixon, J.S., J. Comput.-Aided Mol. Design, 9(1995)113.
Judson, R.S., Tan, Y.T., Mori, E., Melius, C., Jaeger, E.P., Treasurywala, A.M. and Mathiowetz, A., J. Comput. Chem., 16 (1995) 1405.
Clark, K.P. and Ajay, J. Comput. Chem., 16 (1995) 1210.
Jones, G., Willett, P. and Glen, R.C., J. Mol. Biol., 245(1995)43.
Verkhivker, G.M., Rejto, P.A., Gehlhaar, D.K. and Freer, S.T., Proteins Struct. Funct. Genet., 25(1996)342.
McGarrah, D.B. and Judson, R.S., J. Comput. Chem., 14 (1993) 1385.
Judson, R.S., Jaeger, E.P., Treasurywala, A.M. and Peterson, M.L., J. Comput. Chem., 14 (1993) 1407.
Unger, R. and Moult, J., J. Mol. Biol., 231(1993)75.
Sun, S., Protein Sci., 2(1993)762.
Dandekar, T. and Argos, P., Protein Eng., 5(1992)637.
Dandekar, T. and Argos, P., J. Mol. Biol., 236(1994)844.
Fogel, D.B., Evolutionary Computation: Toward a New Philosophy of Machine Intelligence, IEEE Press, Piscataway, NJ, 1995.
Bowie, J.U. and Eisenberg, D., Proc. Natl. Acad. Sci. USA, 91(1994)4436.
Gehlhaar, D.K., Verkhivker, G., Rejto, P.A., Fogel, D.B., Fogel, L.J. and Freer, S.T., In McDonnell, J.R., Reynolds, R.G. and Fogel, D.B. (Eds.) Proceedings of the 4th Annual Conference on Evolutionary Programming, MIT Press, Cambridge, MA, 1995, pp. 615–627.
Gehlhaar, D.K., Verkhivker, G.M., Rejto, P.A., Sherman, C.J., Fogel, D.B., Fogel, L.J. and Freer, S.T., Chem. Biol., 2(1995)317.
Verkhivker, G.M. and Rejto, P.A., Proc. Natl. Acad. Sci. USA, 93(1996)60.
Schwefel, H.-P., Numerical Optimization of Computer Models, Wiley, Chichester, 1981.
Standard deviations of the Gaussian mutations S for each variable were generatedwhere N(0,1) represents a zero-mean, unit variance Gaussian random number, and n is the number of variables in the optimization. Ni(0,1) indicates that a different random numberchosen for each component of the individual. The learning rate T influences the movement of the individual with respect to the parent, while the learning rate t influences- variations between components of the individual. This formula was obtained from Ref. 53.
Press, W.H., Teukolsky, S.A., Vetterling, W.T. and Flannery, B.P., Numerical Recipes in C. The Art of Scientific Computing, Cambridge University Press, Cambridge, 1992.
Yue, K. and Dill, K.A., Protein Sci., 5(1996)254.
Elofsson, A., Le Grand, S.M. and Eisenberg, D., Proteins Struct. Funct. Genet., 23(1995)73.
Gehlhaar, D.K., Moerder, K.E., Zichi, D., Sherman, C.J., Ogden, R.C. and Freer, S.T., J. Med. Chem., 38(1995)466.
Knegtel, R.M.A., Antoon, J., Rullmann, C., Boelens, R. and Kaptein, R., J. Mol. Biol., 235(1994)318.
Mayo, S.L., Olafson, B.D. and Goddard III, W.A., J. Phys. Chem., 94(1990)8897.
Wlodawer, A. and Erickson, J.W., Annu. Rev. Biochem., 62(1993)543.
Appelt, K., Perspect. Drug Discov. Design, 1(1993)23.
Reich, S.H., Melnick, M., Davies II, J.F., Appelt, K., Lewis, K.K., Fuhry, M.A., Pino, M., Trippe, A.J., Nguyen, D., Dawson, H., Wu, B.-W., Musick, L., Kosa, M., Kahil, D., Webber, S., Gehlhaar, D.K., Andrada, D. and Shetty, B., Proc. Natl. Acad. Sci. USA, 92(1995)3298.
Swain, A.L., Miller, M.M., Green, J., Rich, D.H., Schneider, J., Kent, S.B.H. and Wlodawer, A., Proc. Natl. Acad. Sci. USA, 87(1990)8805.
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Rejto, P.A., Verkhivker, G.M., Gehlhaar, D.K., Freer, S.T. (1997). New trends in computational structure prediction of ligand-protein complexes for receptor-based drug design. In: van Gunsteren, W.F., Weiner, P.K., Wilkinson, A.J. (eds) Computer Simulation of Biomolecular Systems. Computer Simulations of Biomolecular Systems, vol 3. Springer, Dordrecht. https://doi.org/10.1007/978-94-017-1120-3_17
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DOI: https://doi.org/10.1007/978-94-017-1120-3_17
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