Letter | Published:

The dead-end elimination theorem and its use in protein side-chain positioning

Naturevolume 356pages539542 (1992) | Download Citation

Subjects

Abstract

THE prediction of a protein's tertiary structure is still a considerable problem because the huge amount of possible conformational space1 makes it computationally difficult. With regard to side-chain modelling, a solution has been attempted by the grouping of side-chain conformations into representative sets of rotamers2–5. Nonetheless, an exhaustive combinatorial search is still limited to carefully identified packing units5,6containing a limited number of residues. For larger systems other strategies had to be develop-ped, such as the Monte Carlo Procedure6,7 and the genetic algorithm and clustering approach8. Here we present a theorem, referred to as the 'dead-end elimination' theorem, which imposes a suitable condition to identify rotamers that cannot be members of the global minimum energy conformation. Application of this theorem effectively controls the computational explosion of the rotamer combinatorial problem, thereby allowing the determination of the global minimum energy conformation of a large collection of side chains.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Levinthal, C. J. chim. Phys. 65, 44–45 (1968).

  2. 2

    McGregor, M. J., Islam, S. A. & Sternberg, M. J. E. J. molec. Biol. 198, 295–310 (1987).

  3. 3

    Janin, J., Wodak, S., Levitt, M. & Maigret, B. J. Molec. Biol. 125, 357–386 (1978).

  4. 4

    James, M. N. G. & Sielecki, A. R. J. J. molec. Biol. 163, 299–361 (1983).

  5. 5

    Ponder, J. W. & Richards, F. M. J. molec. Biol. 193, 775–791 (1987).

  6. 6

    Lee, C. & Levitt, M. Nature 352, 448–451 (1991).

  7. 7

    Holm, L. & Sander, C. J. molec. Biol. 218, 183–194 (1991).

  8. 8

    Tuffery, P., Etchebest, C., Hazout, S. & Lavery, R. J. biomolec. struct. Dyn. 8, 1267–1289 (1991).

  9. 9

    Delhaise, P., Bardiaux, M. & Wodak, S. J. J. molec. Graph. 2, 103–106 (1984).

  10. 10

    Miller, S., Janin, J., Lesk, A. M. & Chothia, C. J. molec. Biol. 196, 641–656 (1987).

  11. 11

    Berenstein, F. C. et al. J. molec. Biol. 112, 535–542 (1977).

  12. 12

    Brooks, B. R. & Karplus, M. J. comput. Chem. 4, 187–217 (1983).

Download references

Author information

Affiliations

  1. Interdisciplinary Research Center, KU Leuven Campus Kortrijk, Kortrijk, B8500, Belgium

    • Johan Desmet
  2. Corvas International NV, Jozef Plateaustraat 22, B9000, Gent, Belgium

    • Marc De Maeyer
    •  & Ignace Lasters
  3. BIOSON Research Institute, Department of Chemistry, Chemical Physics, RU Groningen, Nij'enborgh 16, 9747 AG, Groningen, The Netherlands

    • Bart Hazes

Authors

  1. Search for Johan Desmet in:

  2. Search for Marc De Maeyer in:

  3. Search for Bart Hazes in:

  4. Search for Ignace Lasters in:

About this article

Publication history

Received

Accepted

Issue Date

DOI

https://doi.org/10.1038/356539a0

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.