%0 Generic %A Simoncini, David %A Allouche, David %A Givry, Simon de %A Delmas, Céline %A Barbe, Sophie %A Schiex, Thomas %D 2015 %T Guaranteed Discrete Energy Optimization on Large Protein Design Problems %U https://acs.figshare.com/articles/dataset/Guaranteed_Discrete_Energy_Optimization_on_Large_Protein_Design_Problems/2101636 %R 10.1021/acs.jctc.5b00594.s002 %2 https://ndownloader.figshare.com/files/3734902 %K CPD %K arc consistency %K 1 Rosetta unit %K annealing implementation %K energy threshold %K design sequences %K 66 GB RAM %K rotamer %K Talaris 2014 decomposable energy function %K redesign problems %K Discrete Energy Optimization %K Large Protein Design ProblemsIn Computational Protein Design %K annealing algorithm %K search spaces %X In Computational Protein Design (CPD), assuming a rigid backbone and amino-acid rotamer library, the problem of finding a sequence with an optimal conformation is NP-hard. In this paper, using Dunbrack’s rotamer library and Talaris2014 decomposable energy function, we use an exact deterministic method combining branch and bound, arc consistency, and tree-decomposition to provenly identify the global minimum energy sequence-conformation on full-redesign problems, defining search spaces of size up to 10234. This is achieved on a single core of a standard computing server, requiring a maximum of 66GB RAM. A variant of the algorithm is able to exhaustively enumerate all sequence-conformations within an energy threshold of the optimum. These proven optimal solutions are then used to evaluate the frequencies and amplitudes, in energy and sequence, at which an existing CPD-dedicated simulated annealing implementation may miss the optimum on these full redesign problems. The probability of finding an optimum drops close to 0 very quickly. In the worst case, despite 1,000 repeats, the annealing algorithm remained more than 1 Rosetta unit away from the optimum, leading to design sequences that could differ from the optimal sequence by more than 30% of their amino acids. %I ACS Publications