title: Computational characterization of the sequence landscape in simple protein alphabets.
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.
authors.affiliation: Department of Chemical Engineering, Princeton University, Princeton, NJ 08544, USA. shell@princeton.edu
authors.forename: M Scott
authors.initials: MS
authors.lastname: Shell
authors.forename: Pablo G
authors.initials: PG
authors.lastname: Debenedetti
authors.forename: Athanassios Z
authors.initials: AZ
authors.lastname: Panagiotopoulos
mesh_terms: D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis*; D002352:Carrier Proteins / Q000737:chemistry* / Q000378:metabolism; D007473:Ion Channels / Q000737:chemistry; D008969:Molecular Sequence Data; D011506:Proteins / Q000737:chemistry*; D015203:Reproducibility of Results
chemical_list: D000596:Amino Acids; D002352:Carrier Proteins; D007473:Ion Channels; D011506:Proteins