Identification of computational hot spots in protein interfaces: combining solvent accessibility and inter-residue potentials improves the accuracy.
BACKGROUND
Hot spots are residues comprising only a small fraction of interfaces yet accounting for the majority of the binding energy. These residues are critical in understanding the principles of protein interactions. Experimental studies like alanine scanning mutagenesis require significant effort; therefore, there is a need for computational methods to predict hot spots in protein interfaces.


RESULTS
We present a new intuitive efficient method to determine computational hot spots based on conservation (C), solvent accessibility [accessible surface area (ASA)] and statistical pairwise residue potentials (PP) of the interface residues. Combination of these features is examined in a comprehensive way to study their effect in hot spot detection. The predicted hot spots are observed to match with the experimental hot spots with an accuracy of 70% and a precision of 64% in Alanine Scanning Energetics Database (ASEdb), and accuracy of 70% and a precision of 73% in Binding Interface Database (BID). Several machine learning methods are also applied to predict hot spots. Performance of our empirical approach exceeds learning-based methods and other existing hot spot prediction methods. Residue occlusion from solvent in the complexes and pairwise potentials are found to be the main discriminative features in hot spot prediction.


CONCLUSIONS
Our empirical method is a simple approach in hot spot prediction yet with its high accuracy and computational effectiveness. We believe that this method provides insights for the researchers working on characterization of protein binding sites and design of specific therapeutic agents for protein interactions.


BACKGROUND
The list of training and test sets are available as Supplementary Data at http://prism.ccbb.ku.edu.tr/hotpoint/supplement.doc.


BACKGROUND
Supplementary data are available at Bioinformatics online.
Tuncbag
Nurcan
N
Center for Computational Biology and Bioinformatics and College of Engineering, Koc University, Rumelifeneri Yolu, Sariyer Istanbul, Turkey.
Gursoy
Attila
A
Keskin
Ozlem
O
D000409:Alanine / Q000737:chemistry / Q000378:metabolism; D001665:Binding Sites; D019295:Computational Biology / Q000379:methods; D030562:Databases, Protein; D025941:Protein Interaction Mapping / Q000379:methods*; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism
D011506:Proteins; D000409:Alanine