Computational characterization of the sequence landscape in simple protein alphabets |
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Authors: | Shell M Scott Debenedetti Pablo G Panagiotopoulos Athanassios Z |
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Affiliation: | Department of Chemical Engineering, Princeton University, Princeton, NJ 08544, USA. shell@princeton.edu |
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Abstract: | We characterize the "sequence landscapes" in several simple, heteropolymer models of proteins by examining their mutation properties. Using an efficient flat-histogram Monte Carlo search method, our approach involves determining the distribution in energy of all sequences of a given length when threaded through a common backbone. These calculations are performed for a number of Protein Data Bank structures using two variants of the 20-letter contact potential developed by Miyazawa and Jernigan [Miyazawa S, Jernigan WL. Macromolecules 1985;18:534], and the 2-monomer HP model of Lau and Dill [Lau KF, Dill KA. Macromolecules 1989;22:3986]. Our results indicate significant differences among the energy functions in terms of the "smoothness" of their landscapes. In particular, one of the Miyazawa-Jernigan contact potentials reveals unusual cooperative behavior among its species' interactions, resulting in what is essentially a set of phase transitions in sequence space. Our calculations suggest that model-specific features can have a profound effect on protein design algorithms, and our methods offer a number of ways by which sequence landscapes can be quantified. |
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Keywords: | proteins thermodynamics statistical mechanics landscapes phase transitions Monte Carlo flat‐histogram |
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