Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins
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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2019-09-01
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| Series: | BMC Molecular and Cell Biology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12860-019-0218-z |
| _version_ | 1818174612871053312 |
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| author | Didier Devaurs Dinler A Antunes Sarah Hall-Swan Nicole Mitchell Mark Moll Gregory Lizée Lydia E Kavraki |
| author_facet | Didier Devaurs Dinler A Antunes Sarah Hall-Swan Nicole Mitchell Mark Moll Gregory Lizée Lydia E Kavraki |
| author_sort | Didier Devaurs |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-11T19:47:11Z |
| format | Article |
| id | doaj.art-31d75520ccd24ca6b48f5ab28ef494ca |
| institution | Directory Open Access Journal |
| issn | 2661-8850 |
| language | English |
| last_indexed | 2024-12-11T19:47:11Z |
| publishDate | 2019-09-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Molecular and Cell Biology |
| spelling | doaj.art-31d75520ccd24ca6b48f5ab28ef494ca2022-12-22T00:52:53ZengBMCBMC Molecular and Cell Biology2661-88502019-09-0120111510.1186/s12860-019-0218-zUsing parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteinsDidier Devaurs0Dinler A Antunes1Sarah Hall-Swan2Nicole Mitchell3Mark Moll4Gregory Lizée5Lydia E Kavraki6Department of Computer Science, Rice UniversityDepartment of Computer Science, Rice UniversityDepartment of Computer Science, Rice UniversityDepartment of Computer Science, Rice UniversityDepartment of Computer Science, Rice UniversityDepartment of Melanoma Medical Oncology - Research, The University of Texas MD Anderson Cancer CenterDepartment of Computer Science, Rice UniversityAbstract 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.http://link.springer.com/article/10.1186/s12860-019-0218-zMolecular dockingProtein-ligand dockingProtein-peptide dockingConformational samplingScoringParallelism |
| spellingShingle | Didier Devaurs Dinler A Antunes Sarah Hall-Swan Nicole Mitchell Mark Moll Gregory Lizée Lydia E Kavraki Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins BMC Molecular and Cell Biology Molecular docking Protein-ligand docking Protein-peptide docking Conformational sampling Scoring Parallelism |
| title | Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins |
| title_full | Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins |
| title_fullStr | Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins |
| title_full_unstemmed | Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins |
| title_short | Using parallelized incremental meta-docking can solve the conformational sampling issue when docking large ligands to proteins |
| title_sort | using parallelized incremental meta docking can solve the conformational sampling issue when docking large ligands to proteins |
| topic | Molecular docking Protein-ligand docking Protein-peptide docking Conformational sampling Scoring Parallelism |
| url | http://link.springer.com/article/10.1186/s12860-019-0218-z |
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