Extended connectivity interaction features: improving binding affinity prediction through chemical description

By Norberto Sánchez-Cruz, José L. Medina-Franco, Jordi Mestres, Xavier Barril. 2020

106 citations recorded by the source corpus.

MOTIVATION Machine-learning scoring functions have been found to outperform standard scoring functions for binding affinity prediction of protein-ligand complexes. A plethora of reports focus on the implementation of increasingly complex algorithms, while the chemical description of the system has not been fully exploited. RESULTS Herein, we introduce Extended Connectivity Interaction Features (ECIF) to describe protein-ligand complexes and build machine-learning scoring functions with improved predictions of binding affinity. ECIF are a set of protein-ligand atom-type pair counts that take into account each atom's connectivity to describe it and thus define the pair types. ECIF were used to build different machine-learning models to predict protein-ligand affinities (pKd / pKi). The models were evaluated in terms of "scoring power" on the Comparative Assessment of Scoring Functions 2016. The best models built on ECIF achieved Pearson correlation coefficients of 0.857 when used on its own, and 0.866 when used in combination with ligand descriptors, demonstrating ECIF descriptive power. AVAILABILITY Data and code to reproduce all the results are freely available at https://github.com/DIFACQUIM/ECIF. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.

Subfields: Computational Theory and Mathematics, Molecular Biology

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In Computational Theory and Mathematics

1. Fergus Boyles
2. Charlotte M. Deane
3. Marc A. Moesser
4. Dominik K. Klein
5. Andrew Baxter
6. Garrett M. Morris

In Molecular Biology

1. Fergus Boyles
2. Charlotte M. Deane
3. Marc A. Moesser
4. Dominik K. Klein
5. Andrew Baxter
6. Garrett M. Morris

Citations in the corpus

• Protein-Ligand Interaction Graphs: Learning from Ligand-Shaped 3D Interaction Graphs to Improve Binding Affinity Prediction (2022, methodology): “…RMSE=1.21 / 1.22 for the 5 / 6 Å thresholds, respectively) with no significant advantage of one over the other, which is in line with the results observed by Sánchez-Cruz et al. [8] who found 6 Å to be the optimal threshold for ECIF fingerprints in random forest and gradient boosted tree models.”