Computational characterization of the sequence landscape in simple protein alphabets.
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.
Shell
M Scott
MS
Department of Chemical Engineering, Princeton University, Princeton, NJ 08544, USA. shell@princeton.edu
Debenedetti
Pablo G
PG
Panagiotopoulos
Athanassios Z
AZ
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
D000596:Amino Acids; D002352:Carrier Proteins; D007473:Ion Channels; D011506:Proteins