ProtSA: a web application for calculating sequence specific protein solvent accessibilities in the unfolded ensemble.

Area of Science:

• Biochemistry
• Computational Biology
• Structural Biology

Background:

• Protein stability is governed by thermodynamic changes during folding, linked to solvent accessible surface area.
• Experimental determination of unfolded protein states is challenging, often relying on simplified models.
• Accurate atomic-level solvent accessibilities for unfolded protein ensembles are needed.

Purpose of the Study:

• To develop a web application for calculating sequence-specific solvent accessibilities of protein unfolded states.
• To provide a tool for more accurate estimations of protein folding energetics.

Main Methods:

• The ProtSA web application utilizes the Flexible-Meccano algorithm to generate representative unfolded protein conformations.
• Atomic solvent accessibilities are calculated using the ALPHASURF software.
• Accessibilities are averaged over the generated ensemble to represent the unfolded state.

Main Results:

• ProtSA, a freely available web application, has been developed.
• It calculates sequence-specific solvent accessibilities for protein unfolded state ensembles.
• The tool provides averaged atom solvent accessibilities based on generated conformations.

Conclusions:

• ProtSA is a novel tool for studying protein folding energetics.
• It enables improved estimation of the hydrophobic effect's contribution to folding free energy.
• The tool aids in refining protein folding energetics parameterizations and understanding mutation effects on stability.