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2018/2019

Evaluation of scoring function performance on DNA-ligand complexes

The Open Medicinal Chemistry Journal, 2019(13): 40-49

作者Pedro Fong,
Hong-Kong Wong
摘要

Background: DNA has been a pharmacological target for different types of treatment, such as antibiotics and chemotherapy agents, and is still a potential target in many drug discovery processes. However, most docking and scoring approaches were parameterised for protein-ligand interactions; their suitability for modelling DNA-ligand interactions is uncertain.

 

Objective: This study investigated the performance of four scoring functions on DNA-ligand complexes.

 

Material & Methods: Here, we explored the ability of four docking protocols and scoring functions to discriminate the native pose of 33 DNA-ligand complexes over a compiled set of 200 decoys for each DNA-ligand complexes. The four approaches were the AutoDock, ASP@GOLD, ChemScore@GOLD and GoldScore@GOLD.

 

Results: Our results indicate that AutoDock performed the best when predicting binding mode and that ChemScore@GOLD achieved the best discriminative power. Rescoring of AutoDock-generated decoys with ChemScore@GOLD further enhanced their individual discriminative powers. All four approaches have no discriminative power in some DNA-ligand complexes, including both minor groove binders and intercalators.

 

Conclusion: This study suggests that the evaluation for each DNA-ligand complex should be performed in order to obtain meaningful results for any drug discovery processes. Rescoring with different scoring functions can improve discriminative power.


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