Improved pose and affinity predictions using different protocols tailored on the basis of data availability

Prathipati, Philip; Nagao, Chioko; Ahmad, Shandar; Mizuguchi, Kenji

doi:https://doi.org/10.1007/s10822-016-9982-4

Improved pose and affinity predictions using different protocols tailored on the basis of data availability

Prathipati, Philip; Nagao, Chioko; Ahmad, Shandar et al.

Journal of Computer-Aided Molecular Design, 2016, 30(9), 817-828

Number of Access:216（2025-06-08 13:47 Counts）

Identifier to cite or link to this item: https://hdl.handle.net/11094/79141

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Title	Improved pose and affinity predictions using different protocols tailored on the basis of data availability
Creator	CreatorName Prathipati, Philip
	NRID 1000010402463 1000010402463 researchmap permalink c_nagao c_nagao Scopus Author ID 14520710200 14520710200 ORCID 0000-0002-7721-0642 0000-0002-7721-0642 CreatorName Nagao, Chioko
	CreatorName Ahmad, Shandar
	NRID 1000050450896 1000050450896 ORCID 0000-0003-3021-7078 0000-0003-3021-7078 researchmap permalink kenji_mizuguchi kenji_mizuguchi Scopus Author ID 57191477452 57191477452 CreatorName Mizuguchi, Kenji
Subject	Data-optimal protocol
	Docking
	GLMNET
	Kinetic stability
	QSAR
	Scoring
	Thermodynamic stability
Description	This is a post-peer-review, pre-copyedit version of an article published in Journal of Computer-Aided Molecular Design. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10822-016-9982-4.
Description	Prathipati, P., Nagao, C., Ahmad, S. et al. Improved pose and affinity predictions using different protocols tailored on the basis of data availability. J Comput Aided Mol Des 30, 817–828 (2016). https://doi.org/10.1007/s10822-016-9982-4
Abstract	The D3R 2015 grand drug design challenge provided a set of blinded challenges for evaluating the applicability of our protocols for pose and affinity prediction. In the present study, we report the application of two different strategies for the two D3R protein targets HSP90 and MAP4K4. HSP90 is a well-studied target system with numerous co-crystal structures and SAR data. Furthermore the D3R HSP90 test compounds showed high structural similarity to existing HSP90 inhibitors in BindingDB. Thus, we adopted an integrated docking and scoring approach involving a combination of both pharmacophoric and heavy atom similarity alignments, local minimization and quantitative structure activity relationships modeling, resulting in the reasonable prediction of pose [with the root mean square deviation (RMSD) values of 1.75 Å for mean pose 1, 1.417 Å for the mean best pose and 1.85 Å for the mean all poses] and affinity (ROC AUC = 0.702 at 7.5 pIC50 cut-off and R = 0.45 for 180 compounds). The second protein, MAP4K4, represents a novel system with limited SAR and co-crystal structure data and little structural similarity of the D3R MAP4K4 test compounds to known MAP4K4 ligands. For this system, we implemented an exhaustive pose and affinity prediction protocol involving docking and scoring using the PLANTS software which considers side chain flexibility together with protein–ligand fingerprints analysis assisting in pose prioritization. This protocol through fares poorly in pose prediction (with the RMSD values of 4.346 Å for mean pose 1, 4.69 Å for mean best pose and 4.75 Å for mean all poses) and produced reasonable affinity prediction (AUC = 0.728 at 7.5 pIC50 cut-off and R = 0.67 for 18 compounds, ranked 1st among 80 submissions).
Publisher	Springer International Publishing
Source Title	Journal of Computer-Aided Molecular Design
Volume (Issue)	30(9)
Page	817-828
Date of Issued	2016-10-06
Language	English
Handle URL	https://hdl.handle.net/11094/79141
PISSN	0920654X
eISSN	15734951
NCID	AA10715216
Relation.isVersionOf	DOI (Publisher Version) https://doi.org/10.1007/s10822-016-9982-4
Relation.isIdenticalTo	PMID 27714493
Access Rights	open access
oaire:version	Accepted Manuscript
Category	学術雑誌論文 Journal Article

Resource Type	journal article
Local Type	Journal Article
DCMI Type	Text
DCTERMS.bibliographicCitation	Journal of Computer-Aided Molecular Design. 2016, 30(9), p. 817-828
DC.title	Improved pose and affinity predictions using different protocols tailored on the basis of data availability
DC.creator	Prathipati, Philip
	Nagao, Chioko
	Ahmad, Shandar
	Mizuguchi, Kenji
DC.publisher	Springer International Publishing
DC.language' scheme='DCTERMS.RFC1766	English
DC.type' scheme='DCTERMS.DCMIType	Text
DCTERMS.issued' scheme='DCTERMS.W3CDTF	2016-10-06
DC.identifier	https://doi.org/10.1007/s10822-016-9982-4
DC.subject	Data-optimal protocol
	Docking
	GLMNET
	Kinetic stability
	QSAR
	Scoring
	Thermodynamic stability
DC.description	This is a post-peer-review, pre-copyedit version of an article published in Journal of Computer-Aided Molecular Design. The final authenticated version is available online at: http://dx.doi.org/10.1007/s10822-016-9982-4.
DC.description	Prathipati, P., Nagao, C., Ahmad, S. et al. Improved pose and affinity predictions using different protocols tailored on the basis of data availability. J Comput Aided Mol Des 30, 817–828 (2016). https://doi.org/10.1007/s10822-016-9982-4
DCTERMS.abstract	The D3R 2015 grand drug design challenge provided a set of blinded challenges for evaluating the applicability of our protocols for pose and affinity prediction. In the present study, we report the application of two different strategies for the two D3R protein targets HSP90 and MAP4K4. HSP90 is a well-studied target system with numerous co-crystal structures and SAR data. Furthermore the D3R HSP90 test compounds showed high structural similarity to existing HSP90 inhibitors in BindingDB. Thus, we adopted an integrated docking and scoring approach involving a combination of both pharmacophoric and heavy atom similarity alignments, local minimization and quantitative structure activity relationships modeling, resulting in the reasonable prediction of pose [with the root mean square deviation (RMSD) values of 1.75 Å for mean pose 1, 1.417 Å for the mean best pose and 1.85 Å for the mean all poses] and affinity (ROC AUC = 0.702 at 7.5 pIC50 cut-off and R = 0.45 for 180 compounds). The second protein, MAP4K4, represents a novel system with limited SAR and co-crystal structure data and little structural similarity of the D3R MAP4K4 test compounds to known MAP4K4 ligands. For this system, we implemented an exhaustive pose and affinity prediction protocol involving docking and scoring using the PLANTS software which considers side chain flexibility together with protein–ligand fingerprints analysis assisting in pose prioritization. This protocol through fares poorly in pose prediction (with the RMSD values of 4.346 Å for mean pose 1, 4.69 Å for mean best pose and 4.75 Å for mean all poses) and produced reasonable affinity prediction (AUC = 0.728 at 7.5 pIC50 cut-off and R = 0.67 for 18 compounds, ranked 1st among 80 submissions).
DC.format	79141
citation_title	Improved pose and affinity predictions using different protocols tailored on the basis of data availability
citation_author	Prathipati, Philip
	Nagao, Chioko
	Ahmad, Shandar
	Mizuguchi, Kenji
citation_publisher	Springer International Publishing
citation_language	English
citation_date	2016-10-06
citation_journal_title	Journal of Computer-Aided Molecular Design
citation_volume	30
citation_issue	9
citation_firstpage	817
citation_lastpage	828
citation_doi	https://doi.org/10.1007/s10822-016-9982-4
citation_pmid	27714493
citation_public_url	https://hdl.handle.net/11094/79141

Improved pose and affinity predictions using different protocols tailored on the basis of data availability

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