APIF: A New Interaction Fingerprint Based on Atom Pairs and Its Application to Virtual Screening

Abstract

A new interaction fingerprint (IF) called APIF (atom-pairs-based interaction fingerprint) has been developed for postprocessing protein-ligand docking results. Unlike other existing fingerprints which employ absolute locations of individual interactions, APIF considers the relative positions of pairs of interacting atoms. Docking-based virtual screening was performed with GOLD using the crystal structures of trypsin, rhinovirus, HIV protease, carboxypeptidase, and estrogen receptor-alpha as targets. A score derived from the similarity of the bit strings for each docking solution to that of a known reference binding mode was obtained. Comparisons between APIF, GoldScore function, and standard interaction fingerprint (CHIF) scores were performed using enrichment plots. Superior recovery rates were observed in the IF score cases. Comparable results were achieved by using either of the two interaction fingerprints, substantially improving GoldScore function enrichment factors. Binding mode analyses were also carried out in order to study the best method for selecting conformations with a binding mode similar to that of the reference crystallized complex. These showed that the first conformations retrieved by interaction fingerprint scores had a more similar binding mode to the reference complex than those retrieved by the GoldScore function.

Challenges and advances in computational docking: 2009 in review

“…Several approaches have been tested to improve enrichment in VS, including: application of interaction fingerprints for postprocessing of docking results (91,98,134), consensus (84,86) and QM/MM (79) scoring, combining docking with pharmacophore perception (90,(134)(135)(136)(137)(138) or other ligand-based methods (64,(139)(140)(141), accounting for receptor flexibility (142)(143)(144). and use of machine-learning strategies (67,145).…”

From Activity Cliffs to Target‐Specific Scoring Models and Pharmacophore Hypotheses

“…[9][10][11][12] Furthermore, interaction scores have been shown to be useful descriptors for QSAR-like approaches directly correlating interaction energies with potencies in order to gain interaction-specific weights. An early approach is COMBINE, developed by Wade and colleagues in 1995, [13] which has been successfully applied to various targets.…”

Recent Trends and Observations in the Design of High-Quality Screening Collections

“…Particularly promising developments in the improvement of docking scoring functions are physically more realistic simulations of the binding process, such as considering the desolvation of ligand and binding site [131], flexibility of the receptor using multiple crystal structures [132][133][134][135][136] or short molecular dynamics simulations [137]. An orthogonal development is the consideration of additional target-based knowledge on important interactions, such as in the structural interacting fingerprint (SIFt) approach and related approaches [138][139][140][141], by using co-crystal structure-derived pharmacophore constraints [142,143], or scoring functions optimized for targets and target classes [144][145][146][147][148][149].…”