Abstract
Two major factors have influenced the dramatic growth in the use of computer-modeling techniques as an integral aspect of the drug discovery process. The first of these has been the increased availability of powerful, but relatively inexpensive, computer systems in both academic and industrial research laboratories. This provided researchers with direct access to a level of computational capacity that had previously been available only on large and prohibitively expensive mainframe computers. The second important factor was the availability of high-speed, high-resolution, graphical display systems.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
Similar content being viewed by others
References
Abraham, R. J. and Hudson, B. (1984) Approaches to charge calculations in molocular mechanics. 2. Resonance effects in conjugated systems. J. Comp. Chem. 5, 562–570.
Abraham, R. J. and Parry, K. (1970) Rotational isomerism. VIII. A calculation of the rotational barriers and rotamer energies of some halogenated compounds. J. Chem. Soc. B, 539–545.
Allinger, N. L. (1976) Calculation of molecular structure and energy by force-field methods. Adv. Phys. Org. Chem. 13, 1–82.
Andrews, P. R., Craik, D. J., and Martin, J. L. (1984) Functional group contributions to drug-receptor interactions. J. Med. Chem. 27, 1648–1657.
Armarego, W. L. F., Waring, P., and Williams, J. W. (1980) Absolute configuration of 6-methyl-5,6,7,8-tetrahydropterin produced by enzymatic reduction (dihydrofolate reductase and NADPH) of 6-methyl-7,8-dihydropterin. Chem. Comm. 334–336.
Baird, N. C. and Dewar, M. J. S. (1969) Ground state of sigma-bonded molecules. IV. M.I.N.D.O. method and its application to hydrocarbons. J. Chem. Phys. 50, 1262–1274.
Baker, D. J., Beddell, C. R., Champness, J. N., Goodford, P. J., Norrington, F. E. A., Smith,D. R., and Stammer, D. K. (1981) The binding of trimethoprim to bacterial dihydrofolate reductase. FEBS Lett. 126, 49–52.
Bingham, R. C., Dewar, M. J. S., and Lo, D. H. (1975) Ground states of molecules. XXV. MINDO-3: An improved version of the MINDO semi-empirical SCF-MO method. J. Am. Chem. Soc. 97, 1285–1293.
Binkley, J. S., Frisch, M. J., DeFrees, D. J., Raghavachari, K., Whiteside, R. A., Schlegel, H. B., Fluder, E. M., and Pople, J. A. (1983) GAUSSIAN 82 Carnegie-Mellon University, Pittsburgh, Pennsylvania.
Binkley, J. S., Whiteside, R. A., Krishman, R„ Seeger, R., DeFrees, D. J., Schlegel, H. B., Topiol, S., Kahn, L. R., and Pople, J. A. (1981) QCPE program 406. University of Indiana, Bloomington, Indiana.
Blake, C. C. F. and Oatley, S. J. (1977) Protein-DNA and protein-hormone interactions in prealbumin: A model of the thyroid hormone nuclear receptor. Nature 268, 115–120.
Blake, C. C. F., Geisow, M.J., Oatley, S. J., and Rerat, C. J. (1978) Structure of prealbumin: Secondary, tertiary and quaternary interactions determined by Fourier refinement at 1.8 angstroms. J. Mol. Biol. 121, 339–356.
Blaney, J. M., Jorgenson, E. C., Connolly, M. L., Ferrin, T. E., Langridge, R., Oatley, S. J., Burridge, J. M., and Blake, C. C. F. (1982) Computer graphics in drug design: Molecular modeling of thyroid hormone-prealbumin interactions. J. Med. Chem. 25, 785–790.
Brooks, B. R., Bruccoleri, R. E., Olafson, B. D., States, D. J., Swaminathan, S., and Karplus, M. (1983) CHARMM: A program for macromolecular energy, minimization and dynamics calculations. J. Comp. Chem. 4, 187–217.
Bush, B. L. (1984) Interactive modeling of enzyme-inhibitor complexes at Merck Macromolecular Modeling graphics facility. Comp. Chem. 8, 1–11.
Colwell, W. T., Brown, V. H., Degraw, J. T., and Morrison, N. E. (1979) Inhibition of mycobacterial dihydrofolate reductase by 2,4-diamino-6-alkylpteridines and deazapteridines. Dev. Biochem. 215–218.
Connolly, M. L. (1983a) Solvent-accessible surfaces of proteins and nucleic acids. Science 221, 709–813.
Connolly, M. L. (1983b) Analytical molecular surface calculation. J. Appl. Crystallogr. 16, 548–558.
Del Re, G. (1958) A simple M.O. L.C.A.O. method for calculating the charge distribution in saturated organic molecules. J. Chem. Soc. 4031–4040.
Dewar, M. J. S. and Haselbach, E.)1970) Ground states of sigma-bonded molecules. IX. The MINDO/2 method. J. Am. Chem. Soc. 92, 590–598.
Dewar, M. J. S. and Thiel, W. (1977) Ground states of molecules. 38. The MNDO method. Approximations and parameters. J. Am. Chem. Soc. 99, 4899–4907.
Dupius, M., Rys, J., and King, H. F. (1976) Evaluation of molecular integrals over Gaussian basis functions. J. Chem. Phys. 65, 111–116.
Dupius, M., Spangler, D., and Wendoloski, J. J. (1980) NRCC software catalog 1, program QG01, Lawrence Berkeley Laboratory, University of California, Berkeley, California.
Eberhardt, N. L., Ring, J. C., Latham, K. R., and Baxter, J. D. (1979) Thyroid hormone receptors. Alterations of hormone binding Specificity. J. Biol. Chem. 254, 8534–8539.
Fontecilla-Camps, J. C., Bugg, C. E., Temple Jr., C., Rose, J. D., Montgomery, J. A., and Kisliuk, R. L. (1979) Absolute configuration of biological tetrahvdrofolates. A. crvstallographic determination. J. Am. Chem. Soc. 101, 6114–6115.
Hangaur, D. G., Monzingo, A. F., and Matthews, B. W. (1984) An interactive computer graphics study of thermolysin-catalyzed peptide cleavage and inhibition by N-carboxymethyl dipeptides. Biochemistry 23, 5730–5741.
Hansch, C., Li, R., Blaney, J. M., and Langridge, R. (1982) Comparison of the inhibition of Escherichia coli and Lactobacillus casei dihydrofolate reductase by 2,4-diamino-5-(substituted benzyl) pyrimidines: Quantitative structure-activity relationships, X-ray crystallography and computer graphics in structure-activity analysis. J. Med. Chem. 25, 777–784.
Hendrickson, J. B. (1961) Molecular Geometry. I. Machine computation of the common rings. J. Am. Chem. Soc. 83, 4537–4547.
Hitchings, G. H. and Roth B. (1980) Dihydrofolate Reductases as Targets for Selective Inhibitors, in Enzyme Inhibitors as Drugs ( Sandler, M., ed.) Macmillan, London.
Lifson, S. and Warshel, A. (1968) Consistent force field calculations of conformations, vibrational spectra, and enthalpies of cycloalkane and n-alkane molecules. J. Chem. Phys. 49, 5116–5129.
Matthews, D. A., Alden, R. A., Bolin, J. T., Filman, D. J., Freer, S. T., Suong, R., and Kraut, J. (1978) Dihydrofolate reductase from Lactobacillus casei. X-ray structure of the enzvme-methotrexate-NADPH complex. J. Biol. Chem. 253, 6946–6954.
Matthews, D. A., Alden, R. A., Freer, S. T., Xuong, N. H., and Kraut, J. (1979) Dihydrofolate reductase from Lactobacillus casei. Stereochemistry of NADPH binding. J. Biol. Chem. 254, 4144–4151.
Momany, F. A. (1978) Determination of partial atomic charges from abinitio molecular electrostatic potentials. Application to formamide, methanol and formic acid. J. Phys. Chew. 82, 592–601.
Momany, F. A., McGuire, R. F., Burgess, A. W., and Scheraga, H. A. (1975) Energy parameters in polypeptides. VII. Geometric parameters, partial atomic charges, nonbonded interactions and intrinsic torsional potentials for the naturally occurring amino acids. J. Phys. Chem. 79, 2361–2381.
Monzingo, A. F. and Matthews, B. W. (1984) Binding of N-carboxymethyl dipeptide inhibitors to thermolysin determined by X-ray crystallography: A novel class of transition state analogues for zinc peptidases. Biochemistry 23, 5724–5729.
Morihara, K. and Tsuzuki, H. (1970) Thermolysin: Kinetic study with oligopeptides. Eur. J. Biochem. 15, 374–380.
Mulliken, R. S. (1962) Criteria for the construction of good self-consistent field molecular orbital wave functions, and the significance of L.C.A.O. M.O. population analysis. J. Chem. Phys. 36, 3428–3439.
Pople, J. A. and Gordon, M. (1967) Molecular orbital theory of the electronic structure of organic compounds. I. Substituent effects and dipole moments. J. Am. Chem. Soc. 89, 4253–4261.
Pople, J. A. and Segal, G. A. (1966) Approximate self-consistent molecular orbital theory. III. CNDO results for AB2 and AB3 systems. J. Chem. Phys. 44, 3289–3296.
Pople, J. A., Beveridge, D. L., and Dobosh, P. A. (1967) Approximate self-consistent orbital theory. V. Intermediate neglect of differential overlap. J. Chem. Phys. 47, 2026–2033.
Salama, A. I., Insalaco, J. R., and Maxwell, R. A. (1971) Concerning the molecular requirements for the inhibition of uptake of racemic 3H-norepinephrine into rat cerebral cortex slices by tricyclic antidepressants and related compounds. J. Pharmacol. Exp. Ther. 178, 474–481.
Shotton, D. M. and Watson, H. C. (1970) Three-dimensional structure of tosyl-elastase. Nature 225, 811–816.
Spark, M.J., Winkler, D. A., and Andrews, P. R. (1982) Conformational analysis of folates and folate analogues. Int. J. Quantum Chem., Quantum Biol. Symp. 9, 321–333.
Stewart, J. J. P. and Dewar, M. J. S. (1983) QCPE program 455, University of Indiana, Bloomington, Indiana.
Stolow, R. D., Samal, P. W„ and Giants, T. W. (1981) On CNDO/2—predicted charge alternation. J. Am. Chem. Soc. 103, 197–199.
Watson, H. C., Shotton, D. M., Cox, J. M., and Muirhead, H. (1970) Three-dimensional Fourier synthesis of tosyl-elastase at 3.5 angstrom resolution. Nature 225, 806–811.
Weiner, P. K. and Kollman, P. A. (1981) AMBER: Assisted model building with energy refinement. A general program for modeling molecules and their interactions. J. Comp. Chem. 2, 287–303.
Wiberg, K. B. (1965) A scheme for strain energy minimization. Application to the cycloalkanes. J. Am. Chem. Soc. 87, 1070–1078.
Wiberg, K. B. (1979) Infrared intensities. The methyl halides. Effect of substituents on charge distributions. J. Am. Chem. Soc. 101, 1718–1722.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1987 The Humana Press Inc.
About this chapter
Cite this chapter
Loftus, P., Waldman, M., Hout, R.F. (1987). Computer-Based Approaches to Drug Design. In: Williams, M., Malick, J.B. (eds) Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-4612-4828-6_3
Download citation
DOI: https://doi.org/10.1007/978-1-4612-4828-6_3
Publisher Name: Humana Press
Print ISBN: 978-1-4612-9180-0
Online ISBN: 978-1-4612-4828-6
eBook Packages: Springer Book Archive