Limits...
Amino acid empirical contact energy definitions for fold recognition in the space of contact maps.

Berrera M, Molinari H, Fogolari F - BMC Bioinformatics (2003)

Bottom Line: In 30 out of 35 cases the native structure is correctly recognized and best predictions are usually found among the 10 lowest energy predictions.An important prerequisite for the applicability of the approach is that the protein structure under study should not exhibit anomalous solvent accessibility, compared to soluble proteins whose structure is deposited in the Protein Data Bank.The combined evaluation of a solvent accessibility parameter and contact energy allows for an effective gross screening of predictive models.

View Article: PubMed Central - HTML - PubMed

Affiliation: International School for Advanced Studies Via Beirut 4, 34014 Trieste, Italy. berrera@sissa.it

ABSTRACT

Background: Contradicting evidence has been presented in the literature concerning the effectiveness of empirical contact energies for fold recognition. Empirical contact energies are calculated on the basis of information available from selected protein structures, with respect to a defined reference state, according to the quasi-chemical approximation. Protein-solvent interactions are estimated from residue solvent accessibility.

Results: In the approach presented here, contact energies are derived from the potential of mean force theory, several definitions of contact are examined and their performance in fold recognition is evaluated on sets of decoy structures. The best definition of contact is tested, on a more realistic scenario, on all predictions including sidechains accepted in the CASP4 experiment. In 30 out of 35 cases the native structure is correctly recognized and best predictions are usually found among the 10 lowest energy predictions.

Conclusion: The definition of contact based on van der Waals radii of alpha carbon and side chain heavy atoms is seen to perform better than other definitions involving only alpha carbons, only beta carbons, all heavy atoms or only backbone atoms. An important prerequisite for the applicability of the approach is that the protein structure under study should not exhibit anomalous solvent accessibility, compared to soluble proteins whose structure is deposited in the Protein Data Bank. The combined evaluation of a solvent accessibility parameter and contact energy allows for an effective gross screening of predictive models.

Show MeSH
Energy vs. RMSD for 4rxn 4state decoys The contact energy is plotted against the RMSD from native structure for native structure and all decoy structures with solvent accesibility parameter lower than 0.6 (see text).
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC153506&req=5

Figure 10: Energy vs. RMSD for 4rxn 4state decoys The contact energy is plotted against the RMSD from native structure for native structure and all decoy structures with solvent accesibility parameter lower than 0.6 (see text).

Mentions: The solvent accessibility parameters on these decoys does not allow by itself discrimination of native conformation. Figures 4 to 10 report for each target protein of the set the contact energy per residue versus the RMSD with respect to the native structure. In view of the short length of the chains we chose a rather permissive 0.6 cutoff for the solvent accessibility parameter. Even with such a tolerant filter almost half of the decoys are discarded. For all proteins the native structure is well separated from the decoys. For some, but not for all, of the proteins (namely 2cro and 3icb) a correlation between contact energy and RMSD is apparent from the plot. In all cases, however, among the five lowest energy decoys there is a native-like structure with RMSD lower than 2.0 Å. These results should be compared with the results obtained both with similar approaches and with more refined methods like hybrid molecular mechanics – implicit solvent methods [26,31,29]. The performance of several energy functions tested on an enlarged version of the 4state decoys' set has been afforded by Park and Levitt [5]. It is apparent that the contact definition proposed in the present work has superior capabilities with respect to most similar approaches tested in that study. This is not just depending on cutoff choice for contact definition, because both rank score and z-score for native structure are consistently 1 and ranging between ca. 3.0 and ca. 6.0, respectively, for all cutoff choices, whereas the corresponding z-scores with contact potentials was between ca. 0.5 and ca. 3.0 on the enlarged set of decoys. On the other hand, when we compare our results (Figures 4 to 10) with the corresponding results obtained using the screened Coulomb potential-implicit solvent model (SCP-ISM) [26] or MM/PBSA free energy [31] we notice that with more refined methods a correlation between energy and RMSD from native structure is found which is much less pronounced with contact potentials.


Amino acid empirical contact energy definitions for fold recognition in the space of contact maps.

Berrera M, Molinari H, Fogolari F - BMC Bioinformatics (2003)

Energy vs. RMSD for 4rxn 4state decoys The contact energy is plotted against the RMSD from native structure for native structure and all decoy structures with solvent accesibility parameter lower than 0.6 (see text).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC153506&req=5

Figure 10: Energy vs. RMSD for 4rxn 4state decoys The contact energy is plotted against the RMSD from native structure for native structure and all decoy structures with solvent accesibility parameter lower than 0.6 (see text).
Mentions: The solvent accessibility parameters on these decoys does not allow by itself discrimination of native conformation. Figures 4 to 10 report for each target protein of the set the contact energy per residue versus the RMSD with respect to the native structure. In view of the short length of the chains we chose a rather permissive 0.6 cutoff for the solvent accessibility parameter. Even with such a tolerant filter almost half of the decoys are discarded. For all proteins the native structure is well separated from the decoys. For some, but not for all, of the proteins (namely 2cro and 3icb) a correlation between contact energy and RMSD is apparent from the plot. In all cases, however, among the five lowest energy decoys there is a native-like structure with RMSD lower than 2.0 Å. These results should be compared with the results obtained both with similar approaches and with more refined methods like hybrid molecular mechanics – implicit solvent methods [26,31,29]. The performance of several energy functions tested on an enlarged version of the 4state decoys' set has been afforded by Park and Levitt [5]. It is apparent that the contact definition proposed in the present work has superior capabilities with respect to most similar approaches tested in that study. This is not just depending on cutoff choice for contact definition, because both rank score and z-score for native structure are consistently 1 and ranging between ca. 3.0 and ca. 6.0, respectively, for all cutoff choices, whereas the corresponding z-scores with contact potentials was between ca. 0.5 and ca. 3.0 on the enlarged set of decoys. On the other hand, when we compare our results (Figures 4 to 10) with the corresponding results obtained using the screened Coulomb potential-implicit solvent model (SCP-ISM) [26] or MM/PBSA free energy [31] we notice that with more refined methods a correlation between energy and RMSD from native structure is found which is much less pronounced with contact potentials.

Bottom Line: In 30 out of 35 cases the native structure is correctly recognized and best predictions are usually found among the 10 lowest energy predictions.An important prerequisite for the applicability of the approach is that the protein structure under study should not exhibit anomalous solvent accessibility, compared to soluble proteins whose structure is deposited in the Protein Data Bank.The combined evaluation of a solvent accessibility parameter and contact energy allows for an effective gross screening of predictive models.

View Article: PubMed Central - HTML - PubMed

Affiliation: International School for Advanced Studies Via Beirut 4, 34014 Trieste, Italy. berrera@sissa.it

ABSTRACT

Background: Contradicting evidence has been presented in the literature concerning the effectiveness of empirical contact energies for fold recognition. Empirical contact energies are calculated on the basis of information available from selected protein structures, with respect to a defined reference state, according to the quasi-chemical approximation. Protein-solvent interactions are estimated from residue solvent accessibility.

Results: In the approach presented here, contact energies are derived from the potential of mean force theory, several definitions of contact are examined and their performance in fold recognition is evaluated on sets of decoy structures. The best definition of contact is tested, on a more realistic scenario, on all predictions including sidechains accepted in the CASP4 experiment. In 30 out of 35 cases the native structure is correctly recognized and best predictions are usually found among the 10 lowest energy predictions.

Conclusion: The definition of contact based on van der Waals radii of alpha carbon and side chain heavy atoms is seen to perform better than other definitions involving only alpha carbons, only beta carbons, all heavy atoms or only backbone atoms. An important prerequisite for the applicability of the approach is that the protein structure under study should not exhibit anomalous solvent accessibility, compared to soluble proteins whose structure is deposited in the Protein Data Bank. The combined evaluation of a solvent accessibility parameter and contact energy allows for an effective gross screening of predictive models.

Show MeSH