title: Compressed images for affinity prediction-2 (CIFAP-2): an improved machine learning methodology on protein-ligand interactions based on a study on caspase 3 inhibitors.
abstract: The aim of this study is to propose an improved computational methodology, which is called Compressed Images for Affinity Prediction-2 (CIFAP-2) to predict binding affinities of structurally related protein-ligand complexes. CIFAP-2 method is established based on a protein-ligand model from which computational affinity information is obtained by utilizing 2D electrostatic potential images determined for the binding site of protein-ligand complexes. The quality of the prediction of the CIFAP-2 algorithm was tested using partial least squares regression (PLSR) as well as support vector regression (SVR) and adaptive neuro-fuzzy ınference system (ANFIS), which are highly promising prediction methods in drug design. CIFAP-2 was applied on a protein-ligand complex system involving Caspase 3 (CASP3) and its 35 inhibitors possessing a common isatin sulfonamide pharmacophore. As a result, PLSR affinity prediction for the CASP3-ligand complexes gave rise to the most consistent information with reported empirical binding affinities (pIC(50)) of the CASP3 inhibitors.
authors.affiliation: a Department of Computer Engineering , Middle East Technical University , Ankara , Turkey .
authors.forename: Ozlem
authors.initials: O
authors.lastname: Erdas
authors.forename: Cenk A
authors.initials: CA
authors.lastname: Andac
authors.forename: A Selen
authors.initials: AS
authors.lastname: Gurkan-Alp
authors.forename: Ferda Nur
authors.initials: FN
authors.lastname: Alpaslan
authors.forename: Erdem
authors.initials: E
authors.lastname: Buyukbingol
mesh_terms: D053148:Caspase 3 / Q000737:chemistry* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008024:Ligands; D000069550:Machine Learning; D015394:Molecular Structure; D012044:Regression Analysis; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D008024:Ligands; D013449:Sulfonamides; C505407:CASP3 protein, human; D053148:Caspase 3
keywords: Adaptive neuro-fuzzy inference system; partial least squares regression; sequential floating forward selection; support vector regression