Short-range conformational energies, secondary structure propensities, and recognition of correct sequence-structure matches

✍ Scribed by I. Bahar; M. Kaplan; R.L. Jernigan

• Publisher: John Wiley and Sons
• Year: 1997
• Tongue: English
• Weight: 356 KB
• Volume: 29
• Category: Article
• ISSN: 0887-3585
• DOI: 10.1002/(sici)1097-0134(199711)29:3<292::aid-prot4>3.0.co;2-d

✦ Synopsis

A statistical analysis of known structures is made for an assessment of the utility of short-range energy considerations. For each type of amino acid, the potentials governing (1) the torsions and bond angle changes of virtual C ␣ -C ␣ bonds and (2) the coupling between torsion and bond angle changes are derived. These contribute approximately ؊2 RT per residue to the stability of native proteins, approximately half of which is due to coupling effects. The torsional potentials for the ␣-helical states of different residues are verified to be strongly correlated with the free-energy change measurements made upon single-site mutations at solvent-exposed regions. Likewise, a satisfactory correlation is shown between the ␤-sheet potentials of different amino acids and the scales from freeenergy measurements, despite the role of tertiary context in stabilizing ␤-sheets. Furthermore, there is excellent agreement between our residue-specific potentials for ␣-helical state and other thermodynamic based scales. Threading experiments performed by using an inverse folding protocol show that 50 of 62 test structures correctly recognize their native sequence on the basis of short-range potentials. The performance is improved to 55, upon simultaneous consideration of short-range potentials and the nonbonded interaction potentials between sequentially distant residues. Interactions between near residues along the primary structure, i.e., the local or short-range interactions, are known to be insufficient, alone, for understanding the tertiary structural preferences of proteins alone. Yet, knowledge of shortrange conformational potentials permits rationalizing the secondary structure propensities and aids in the discrimination between correct and incorrecttertiaryfolds.Proteins29:292-308,1997.