Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins
Devaurs, Didier and Antunes, Dinler A and Hall-Swan, Sarah and Mitchell, Nicole and Moll, Mark and Lizée, Gregory and Kavraki, Lydia E (2019) Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins. BMC Molecular and Cell Biology, 20 (1). 42. ISSN 2661-8850 (https://doi.org/10.1186/s12860-019-0218-z)
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Abstract
Background: Docking large ligands, and especially peptides, to protein receptors is still considered a challenge in computational structural biology. Besides the issue of accurately scoring the binding modes of a protein-ligand complex produced by a molecular docking tool, the conformational sampling of a large ligand is also often considered a challenge because of its underlying combinatorial complexity. In this study, we evaluate the impact of using parallelized and incremental paradigms on the accuracy and performance of conformational sampling when docking large ligands. We use five datasets of protein-ligand complexes involving ligands that could not be accurately docked by classical protein-ligand docking tools in previous similar studies. Results: Our computational evaluation shows that simply increasing the amount of conformational sampling performed by a protein-ligand docking tool, such as Vina, by running it for longer is rarely beneficial. Instead, it is more efficient and advantageous to run several short instances of this docking tool in parallel and group their results together, in a straightforward parallelized docking protocol. Even greater accuracy and efficiency are achieved by our parallelized incremental meta-docking tool, DINC, showing the additional benefits of its incremental paradigm. Using DINC, we could accurately reproduce the vast majority of the protein-ligand complexes we considered. Conclusions: Our study suggests that, even when trying to dock large ligands to proteins, the conformational sampling of the ligand should no longer be considered an issue, as simple docking protocols using existing tools can solve it. Therefore, scoring should currently be regarded as the biggest unmet challenge in molecular docking.
ORCID iDs
Devaurs, Didier![ORCID logo](/images/orcid_16x16.png)
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Item type: Article ID code: 90237 Dates: DateEvent5 September 2019Published8 August 2019AcceptedSubjects: Science > Natural history > Biology Department: Faculty of Science > Computer and Information Sciences Depositing user: Pure Administrator Date deposited: 13 Aug 2024 15:19 Last modified: 01 Sep 2024 01:49 Related URLs: URI: https://strathprints.strath.ac.uk/id/eprint/90237