Prediction of protein side chain conformations: a study on the influence of backbone accuracy on conformation stability in the rotamer space.
We have studied the effect of backbone inaccuracy on the efficiency of protein side chain conformation prediction using rotamer libraries. The backbones were generated by randomly perturbing the crystallographic conformation of 12 proteins and exhibit C alpha r.m.s.d.s of up to 2 A. Our results show that, even for a perturbation of the backbone fully compatible with the temperature factors of the proteins, the predicted side chain conformations of approximately 10% of the buried side chains remain variable. This fraction increases further for larger backbone deviations. However, for backbone deviations of up to 2 A r.m.s.d., the predicted side chain r.m.s.d. varies only in a ratio of < 1.4. Moreover, a possible strategy for obtaining side chain conformations close to the experimental ones consists of extracting the consensus conformations of the side chains from a series of backbone conformations. Such a procedure allows the computation of the side chain conformations with no loss of accuracy for backbones exhibiting r.m.s.d.s of up to 1 A from the crystallographic coordinates. For larger backbone deviations (up to 2 A r.m.s.d.) the r.m.s.d. of the buried side chains increases from 1.33 up to 1.60 A. We also discuss the influence of the size of the rotamer library on the quality of the prediction.
Tufféry
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U155 INSERM, Centre de Bioinformatique, Université Paris 7, France.
Etchebest
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Hazout
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D018360:Crystallography, X-Ray; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation