Résumé
Background: The stability of proteins is governed by the heat capacity, enthalpy and entropy changes of folding, which are strongly correlated to the change in solvent accessible surface area experienced by the polypeptide. While the surface exposed in the folded state can be easily determined, accessibilities for the unfolded state at the atomic level cannot be obtained experimentally and are typically estimated using simplistic models of the unfolded ensemble. A web application providing realistic accessibilities of the unfolded ensemble of a given protein at the atomic level will prove useful.
Results: ProtSA, a web application that calculates sequence-specific solvent accessibilities of the unfolded state ensembles of proteins has been developed and made freely available to the scientific community. The input is the amino acid sequence of the protein of interest. ProtSA follows a previously published calculation protocol which uses the Flexible-Meccano algorithm to generate unfolded conformations representative of the unfolded ensemble of the protein, and uses the exact analytical software ALPHASURF to calculate atom solvent accessibilities, which are averaged on the ensemble.
Conclusion: ProtSA is a novel tool for the researcher investigating protein folding energetics. The sequence specific atom accessibilities provided by ProtSA will allow obtaining better estimates of the contribution of the hydrophobic effect to the free energy of folding, will help to refine existing parameterizations of protein folding energetics, and will be useful to understand the influence of point mutations on protein stability.