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

Naturevolume 356pages539542 (1992) | Download Citation



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.

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  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


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