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A quantum mechanics-based halogen bonding scoring function for protein-ligand interactions

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Abstract

A quantum mechanics-based scoring function for halogen bonding interaction, namely XBScoreQM, is developed based on 18,135 sets of geometrical and energetical parameters optimized at M06-2X/aug-cc-pVDZ level. Applying the function on typical halogen bonding systems from Protein Data Bank demonstrates its strong ability of predicting halogen bonding as attractive interaction with strength up to −4 kcal mol−1. With a diverse set of proteins complexed with halogenated ligands, a systematic evaluation demonstrates the integrative advantage of XBScoreQM over 12 other scoring functions on halogen bonding in four aspects, viz. pseudo docking power, ranking power, scoring power, and genuine docking power. Thus, this study not only provides a practicable scoring function of halogen bonding for high throughput virtual screening, but also serves as a benchmark for evaluating the performance of current scoring functions on characterizing halogen bonding.

Derived halogen bonding interaction energy landscape

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Acknowledgments

This work was supported by NNSF (81273435,81302699), Ministry of Science and Technology (2012AA01A305), and International Science and Technology Cooperation Program of China (2014DFA31130).

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Correspondence to Weiliang Zhu.

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ESM 1

Table S1 lists the PDB codes of all the test sets. Table S2 lists the RMSDs between the crystal conformation and the docked conformation with the lowest energy by D3DOCKxb and AutoDock on TestSet-S1. Table S3 lists the predicted energies of the halogen bonds in the complexes of TestSet-S1 by AutoDock and XBScoreQM. Figure S1 is the XBScoreQM-guided docking result for 1zog. Figure S2 is the XBScoreQM-guided docking result for 2aov. Figure S3 is the XBScoreQM-guided docking result for 2gss. Figure S4 is the XBScoreQM-guided docking result for 3kmy. Figure S5 is the XBScoreQM-guided docking result for 3lbk. Figure S6 is the XBScoreQM-guided docking result for 3p9t. Figure S7 is the XBScoreQM-guided docking result for 3r4m. Figure S8 is the XBScoreQM-guided docking result for 2oxd. Figure S9 is the XBScoreQM-guided docking result for 2oxx. Figure S10 is the XBScoreQM-guided docking result for 3kku. Figure S11 is the heat maps of the correlations between the ranking powers of each two scoring functions on the optimized complexes. Dataset S1 lists the intercorrelations between any two of scoring functions with correlation coefficient cutoff ≥ 80% on eight categories with respect to ranking power. (DOCX 5644 kb)

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Yang, Z., Liu, Y., Chen, Z. et al. A quantum mechanics-based halogen bonding scoring function for protein-ligand interactions. J Mol Model 21, 138 (2015). https://doi.org/10.1007/s00894-015-2681-6

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