Abstract：
:The growing number of protein-ligand complex structures, particularly the structures of proteins co-bound with different ligands, in the Protein Data Bank helps us tackle two major challenges in molecular docking studies: the protein flexibility and the scoring function. Here, we introduced a systematic strategy by using the information embedded in the known protein-ligand complex structures to improve both binding mode and binding affinity predictions. Specifically, a ligand similarity calculation method was employed to search a receptor structure with a bound ligand sharing high similarity with the query ligand for the docking use. The strategy was applied to the two datasets (HSP90 and MAP4K4) in recent D3R Grand Challenge 2015. In addition, for the HSP90 dataset, a system-specific scoring function (ITScore2_hsp90) was generated by recalibrating our statistical potential-based scoring function (ITScore2) using the known protein-ligand complex structures and the statistical mechanics-based iterative method. For the HSP90 dataset, better performances were achieved for both binding mode and binding affinity predictions comparing with the original ITScore2 and with ensemble docking. For the MAP4K4 dataset, although there were only eight known protein-ligand complex structures, our docking strategy achieved a comparable performance with ensemble docking. Our method for receptor conformational selection and iterative method for the development of system-specific statistical potential-based scoring functions can be easily applied to other protein targets that have a number of protein-ligand complex structures available to improve predictions on binding.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Xu X,Yan C,Zou Xdoi
10.1007/s10822-017-0038-1subject
Has Abstractpub_date
2017-08-01 00:00:00pages
689-699issue
8eissn
0920-654Xissn
1573-4951pii
10.1007/s10822-017-0038-1journal_volume
31pub_type
杂志文章abstract：:4-(Phenylamino)-pyrrolo[2,1-f][1,2,4]triazines have been discovered as inhibitors of p38alpha. Experimental assays have proven that the configuration of alpha-Me-benzyl connected with amide at C6 is essential for the binding affinity. The S-configured inhibitor (11j) displays 80 times more potency than the R-configure...
journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9740-4
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00126219
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00129748
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/s10822-005-9014-2
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/s10822-004-2722-1
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journal_title：Journal of computer-aided molecular design
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更新日期：2004-11-01 00:00:00
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/s10822-007-9156-5
更新日期：2008-09-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00124347
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/b:jcam.0000021834.50768.c6
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008036526741
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/s10822-015-9887-7
更新日期：2016-01-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-013-9665-3
更新日期：2013-07-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00129749
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/BF00124387
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/s10822-012-9620-8
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/s10822-018-0126-x
更新日期：2018-07-01 00:00:00
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
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更新日期：2017-07-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00124472
更新日期：1996-10-01 00:00:00
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/s10822-006-9055-1
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-005-4789-8
更新日期：2005-04-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-012-9632-4
更新日期：2013-02-01 00:00:00
