| Abstract
| - We present a novel approach to the protein sequence design problem. Given a target native structure and atarget temperature (TD), our method generates sequences for which the target structure is most likely to bethe lowest energy structure. Furthermore, the target structure is rapidly reached at TD. Thus, the simultaneousrequirements of stability and kinetic accessibility are satisfied in our design algorithm. The method consistsof optimizing a function that captures the energy-landscape features responsible for the native state stabilityand folding kinetics of protein-like heteropolymers. The efficacy of our method is demonstrated by applicationsto lattice models (with and without side chains) in which the interaction energies involve pair potentials. Theoptimization process is computationally efficient. Optimal sequences satisfy the relation TD ≈ Tθ, where Tθis the collapse transition temperature.
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