Abstract
To estimate how extensively the ensemble of denatured-state conformations is constrained by local side-chain-backbone interactions, propensities of each of the 20 amino acids to occur in mono- and dipeptides mapped to discrete regions of the Ramachandran map are computed from proteins of known structure. In addition, propensities are computed for the trans, gauche-, and gauche+ rotamers, with or without consideration of the values of phi and psi. These propensities are used in scoring functions for fragment threading, which estimates the energetic favorability of fragments of protein sequence to adopt the native conformation as opposed to hundreds of thousands of incorrect conformations. As finer subdivisions of the Ramachandran plot, neighboring residue phi/psi angles, and rotamers are incorporated, scoring functions become better at ranking the native conformation as the most favorable. With the best composite propensity function, the native structure can be distinguished from 300,000 incorrect structures for 71% of the 2130 arbitrary protein segments of length 40, 48% of 2247 segments of length 30, and 20% of 2368 segments of length 20. A majority of fragments of length 30-40 are estimated to be folded into the native conformation a substantial fraction of the time. These data suggest that the variations observed in amino acid frequencies in different phi/psi/chil environments in folded proteins reflect energetically important local side-chain-backbone interactions, interactions that may severely restrict the ensemble of conformations populated in the denatured state to a relatively small subset with nativelike structure.
Original language | English (US) |
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Pages (from-to) | 18-26 |
Number of pages | 9 |
Journal | Protein Science |
Volume | 11 |
Issue number | 1 |
DOIs | |
State | Published - 2002 |
Keywords
- Amino acid propensities
- Denatured state
- Ramachandran plot
- Rotamers
- Side-chain-backbone interactions
- Threading
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology