Nature 356, 539 - 542 (09 April 1992); doi:10.1038/356539a0

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

Johan Desmet^*, Marc De  Maeyer^†, Bart Hazes^‡ & Ignace Lasters^†

^*Interdisciplinary Research Center, KU Leuven Campus Kortrijk, B8500 Kortrijk, Belgium
^† Corvas International NV, Jozef Plateaustraat 22, B9000 Gent, Belgium
^‡ BIOSON Research Institute, Department of Chemistry, Chemical Physics, RU Groningen, Nij'enborgh 16, 9747 AG Groningen, The Netherlands

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 rotamers^2–5. Nonetheless, an exhaustive combinatorial search is still limited to carefully identified packing units^5,6containing a limited number of residues. For larger systems other strategies had to be develop-ped, such as the Monte Carlo Procedure^6,7 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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