A Review of Methods Available to Estimate Solvent-Accessible Surface Areas of Soluble Proteins in the Folded and Unfolded States

Abstract

Solvent accessible surface area (SASA) of proteins has always been considered as a decisive factor in protein folding and stability studies. It is defined as the surface characterized around a protein by a hypothetical centre of a solvent sphere with the van der Waals contact surface of the molecule. Based on SASA values, amino acid residues of a protein can be classified as buried or exposed. There are various types of SASAs starting from relative solvent accessibility to absolute surface areas. Direct estimation of accurate SASAs of folded proteins experimentally at the atomic level is not possible. However, the SASA of a native protein can be estimated computationally from the atomic coordinates. Similarly, various simulation methods are available to compute the SASA of a protein in its unfolded state. In efforts to estimate the changes in SASA related to the protein folding, a number of the unfolded state models have been proposed. In this review, we have summarized different algorithms and computational tools for SASA estimations. Furthermore, online resources for SASA calculations and representations have also been discussed in detail. This review will be useful for protein chemists and biologists for the accurate measurements of SASA and its subsequent applications for the calculation of various biophysical and thermodynamic properties of proteins.

Rapid in vitro screening for the location‐dependent effects of unnatural amino acids on protein expression and activity

“…Obtained values agreed well with calculations by another calculation method (Cavallo et al, 2003). These and other SASA-predicting algorithms have shown accuracy and agreement in a model-independent manner for folded proteins (Ausaf Ali et al, 2014).…”

Identification of High-Affinity Inhibitors of Cyclin-Dependent Kinase 2 Towards Anticancer Therapy

“…Solvent accessible surface area (SASA) of a protein is the area that directly interacts with its surrounding solvent [38,39]. The SASA of a protein is directly interrelated to its R g .…”

Deciphering the canonical blockade of activated Hageman factor (FXIIa) by benzamidine in the coagulation cascade: A thorough dynamical perspective

“…This is due to the inconsequential differences of ~0.1 Å observed in the RoG estimates for the unbound and BEN‐bound systems. The restrictive effect on the conformation of the catalytic pocket was also determined by estimation of the solvent accessible surface area (SASA), which is able to predict the motion or transition of residues with respect to exposure to the protein environment from a buried hydrophobic region (Ali, Hassan, Islam, & Ahmad, ; Durham, Dorr, Woetzel, Staritzbichler, & Meiler, ; Richmond, ). As shown in Figure , while the catalytic pocket of unbound FXIIa exhibited a high surface exposure, the presence of BEN at the catalytic region retained residual orientation in the buried hydrophobic core with a considerably lower exposure to the surface region.…”

“…This is due to the inconsequential differences of ~0.1 Å observed in the RoG estimates for the unbound and BEN-bound systems. The restrictive effect on the conformation of the catalytic pocket was also determined by estimation of the solvent accessible surface area (SASA), which is able to predict the motion or transition of residues with respect to exposure to the protein environment from a buried hydrophobic region (Ali, Hassan, Islam, & Ahmad, 2014;Durham, Dorr, Woetzel, Staritzbichler, & Meiler, 2009;Richmond, 1984). As shown…”