Solvent-accessible surface area: How well can be applied to hot-spot detection?

• Published in: Proteins, structure, function, and bioinformatics Vol. 82; no. 3; pp. 479 - 490
• Main Authors: Martins, João M., Ramos, Rui M., Pimenta, António C., Moreira, Irina S.
• Format: Journal Article
• Language: English
• Published: United States Blackwell Publishing Ltd 01.03.2014; Wiley Subscription Services, Inc
• Subjects: Bioinformatics; computational alanine scanning mutagenesis; Computational Biology - methods; Databases, Protein; feature based algorithms; hot-spot; Molecular Dynamics Simulation; Proteins - chemistry; solvent accessible surface area; Solvents; Solvents - chemistry; Support Vector Machine; Surface area; Surface Properties; Thermodynamics; feature based algorithms; hot-spot; support vector machine; solvent accessible surface area; computational alanine scanning mutagenesis
• ISSN: 0887-3585; 1097-0134; 1097-0134
• DOI: 10.1002/prot.24413

ABSTRACT A detailed comprehension of protein‐based interfaces is essential for the rational drug development. One of the key features of these interfaces is their solvent accessible surface area profile. With that in mind, we tested a group of 12 SASA‐based features for their ability to correlate and differentiate hot‐ and null‐spots. These were tested in three different data sets, explicit water MD, implicit water MD, and static PDB structure. We found no discernible improvement with the use of more comprehensive data sets obtained from molecular dynamics. The features tested were shown to be capable of discerning between hot‐ and null‐spots, while presenting low correlations. Residue standardization such as relSASAi or rel/resSASAi, improved the features as a tool to predict ΔΔGbinding values. A new method using support machine learning algorithms was developed: SBHD (Sasa‐Based Hot‐spot Detection). This method presents a precision, recall, and F1 score of 0.72, 0.81, and 0.76 for the training set and 0.91, 0.73, and 0.81 for an independent test set. Proteins 2014; 82:479–490. © 2013 Wiley Periodicals, Inc.