Statistical dictionaries for hypothetical in silico model of the early-stage intermediate in protein folding

Abstract

The polypeptide chain folding process appears to be a multi-stage phenomenon. The scientific community has recently devoted much attention to early stages of this process, with numerous attempts at simulating them--either experimentally or in silico. This paper presents a comparative analysis of the predicted and observed results of folding simulations. The proposed technique, based on statistical dictionaries, yields a global accuracy of 57%--a marked improvement over older approaches (with an accuracy of approximately 46%).

Fig. 1

Conformational subspace represented by an elliptical path on the Ramachandran plot (gray line), with areas corresponding to local probability distribution maxima of (φ _e, ψ _e) angle pairs obtained through minimum-distance projections (black lines). The black arrow depicts a sample projection (φ _i, ψ _i) → (φ _ei, ψ _ei)

Fig. 2

Probability distribution profiles for (φ _e, ψ _e) values for histidine, along with structural codes corresponding to individual maxima. The t parameter traverses the elliptical path starting with one of its poles which is located in the bottom right-hand corner of the Ramachandran plot. Bars represent the specific placement of all seven probability maxima which are used to express the early stage intermediate structure

Fig. 3

Comparison of prediction accuracy between statistical dictionaries method (DIC) and contingency table approach (based on the Maximum Probability in contingency table—MP) for amino acid residues and individual structural codes. The list of residues is given on the bottom line. The zones on Ramachandran map is represented according to symbols a–g. The c—represents the helical area, e and f the β-structural forms and g—left helical area. The codes a, b and d traditionally are treated as Random Coil

Fig. 4

2VBL structure (A chain) a native structure derived from PDB, b structure obtained by projecting each (φ, ψ) angle pair onto the elliptical path which represents the ES conformational subspace, c ES structure obtained using the statistical dictionary method, d ES structure obtained using the contingency table method. Blue, red and green fragments correspond to residues which form α-helixes, β-twists and loops respectively. Source: PyMOL

Fig. 5

2JEK structure (A chain) a native structure derived from PDB, b structure obtained by projecting each (φ, ψ) angle pair onto the elliptical path which represents the ES conformational subspace, c ES structure obtained using the statistical dictionary method, d ES structure obtained using the contingency table method. Blue, red and green fragments correspond to residues which form α-helixes, β-twists and loops respectively. Source: PyMOL

Fig. 6

2VAD structure (A chain) a native structure derived from PDB, b structure obtained by projecting each (φ, ψ) angle pair onto the elliptical path which represents the ES conformational subspace, c ES structure obtained using the statistical dictionary method, d ES structure obtained using the contingency table method. Blue, red and green fragments correspond to residues which form α-helixes, β-twists and loops respectively. Source: PyMOL