Computational estimation of specific side chain interaction energies in alpha helices

Fisinger, S Serrano, L Lacroix, E

S. Fisinger et al., Computational estimation of specific side chain interaction energies in alpha helices, PROTEIN SCI, 10(4), 2001, pp. 809-818

32

INGLESE

Article

Biochemistry & Biophysics

PROTEIN SCIENCE

0961-8368 → ACNP

10

4

2001

809 - 818

ISI

0961-8368(200104)10:4<809:CEOSSC>2.0.ZU;2-5

We have used a structure energy-based computer program developed for protei n design, Perla, to provide theoretical estimates of all specific side chai n-side chain interaction energies occurring in cr helices. The computed sid e chain-side chain interaction energies were used as substitutes for the co rresponding values used by the helix/coil transition algorithm, AGADIR. Pre dictions of peptide helical contents were nearly as successful as those obt ained with the originally calibrated set of parameters; a correlation to ex perimentally observed a-helical populations of 0.91 proved that our theoret ical estimates are reasonably correct for amino acid pairs that are frequen t in our database of peptides. Furthermore, we have determined experimental ly the previously uncharacterized interaction energies for Lys-Ile, Thr-Ile , and Phe-Ile amino acid pairs at i,i + 4 positions. The experimental value s compare favorably with the computed theoretical estimates. Importantly, t he computed values for Thr-Ile and Phe-Ile interactions are better than the energies based on chemical similarity, whereas for Lys-Ile they are simila r. Thus, computational techniques can be used to provide precise energies f or amino acid pairwise interactions, a fact that supports the development o f structure energy-based computational tools for structure predictions and sequence design.