Abstract：
:While it may seem intuitive that using an ensemble of multiple conformations of a receptor in structure-based virtual screening experiments would necessarily yield improved enrichment of actives relative to using just a single receptor, it turns out that at least in the p38 MAP kinase model system studied here, a very large majority of all possible ensembles do not yield improved enrichment of actives. However, there are combinations of receptor structures that do lead to improved enrichment results. We present here a method to select the ensembles that produce the best enrichments that does not rely on knowledge of active compounds or sophisticated analyses of the 3D receptor structures. In the system studied here, the small fraction of ensembles of up to 3 receptors that do yield good enrichments of actives were identified by selecting ensembles that have the best mean GlideScore for the top 1% of the docked ligands in a database screen of actives and drug-like "decoy" ligands. Ensembles of two receptors identified using this mean GlideScore metric generally outperform single receptors, while ensembles of three receptors identified using this metric consistently give optimal enrichment factors in which, for example, 40% of the known actives outrank all the other ligands in the database.
journal_name
J Comput Aided Mol Desjournal_title
Journal of computer-aided molecular designauthors
Rao S,Sanschagrin PC,Greenwood JR,Repasky MP,Sherman W,Farid Rdoi
10.1007/s10822-008-9182-ysubject
Has Abstractpub_date
2008-09-01 00:00:00pages
621-7issue
9eissn
0920-654Xissn
1573-4951journal_volume
22pub_type
杂志文章abstract：:Aligning and overlaying two or more bio-active molecules is one of the key tasks in computational drug discovery and bio-activity prediction. Especially chemical-functional molecule characteristics from the view point of a macromolecular target represented as a 3D pharmacophore are the most interesting similarity meas...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-006-9078-7
更新日期：2006-12-01 00:00:00
abstract：:An evolutionary algorithm was developed for fragment-based de novo design of molecules (TOPAS, TOPology-Assigning System). This stochastic method aims at generating a novel molecular structure mimicking a template structure. A set of approximately 25,000 fragment structures serves as the building block supply, which w...
journal_title：Journal of computer-aided molecular design
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doi：10.1023/a:1008184403558
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-019-00195-y
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journal_title：Journal of computer-aided molecular design
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doi：10.1007/s10822-019-00211-1
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abstract：:Crystal structures of the 1,4-dihydropyridine (1,4-DHP) calcium channel activators Bay K 8643 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-nitrophenyl)-pyridine-5-carboxy lat e], Bay O 8495 [methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(3-trifluoromethylphenyl)-pyridine-5- carboxylate], and Bay O 9507 [methyl 1,4-dihydr...
journal_title：Journal of computer-aided molecular design
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doi：10.1007/BF00129749
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abstract：:In the 1960s, the kappa statistic was introduced for the estimation of chance agreement in inter- and intra-rater reliability studies. The kappa statistic was strongly pushed by the medical field where it could be successfully applied via analyzing diagnoses of identical patient groups. Kappa is well suited for classi...
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
doi：10.1007/s10822-009-9315-y
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journal_title：Journal of computer-aided molecular design
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更新日期：2007-10-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-015-9890-z
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：10.1023/b:jcam.0000005754.24588.a0
更新日期：2003-09-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1008197913568
更新日期：2001-02-01 00:00:00
abstract：:A series of non-peptide angiotensin II receptor antagonists was investigated with the aim of developing a 3D QSAR model using comparative molecular field analysis descriptors and approaches. The main goals of the study were dictated by an interest in methodologies and an understanding of the binding requirements to th...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00134180
更新日期：1996-12-01 00:00:00
abstract：:Quantitative Structure-Activity Relationship (QSAR) models are critical in various areas of drug discovery, for example in lead optimisation and virtual screening. Recently, the need for models that are not only predictive but also interpretable has been highlighted. In this paper, a new methodology is proposed to bui...
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：10.1023/a:1023813504011
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-008-9191-x
更新日期：2008-06-01 00:00:00
abstract：:Non-canonical base pairs contribute immensely to the structural and functional variability of RNA, which calls for a detailed characterization of their spatial conformation. Intra-base pair parameters, namely propeller, buckle, open-angle, stagger, shear and stretch describe structure of base pairs indicating planarit...
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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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00355046
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1023/a:1007973008558
更新日期：1998-01-01 00:00:00
abstract：:Virtual Ligand Screening (VLS) has become an integral part of the drug discovery process for many pharmaceutical companies. Ligand similarity searches provide a very powerful method of screening large databases of ligands to identify possible hits. If these hits belong to new chemotypes the method is deemed even more ...
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/s10822-017-0085-7
更新日期：2018-01-01 00:00:00
abstract：:We used blind predictions of the 47 hydration free energies in the SAMPL4 challenge to test multiple partial charge models in the context of explicit solvent free energy simulations with the general AMBER force field. One of the partial charge models, IPolQ-Mod, is a fast continuum solvent-based implementation of the ...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/s10822-014-9714-6
更新日期：2014-03-01 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
pub_type： 杂志文章
doi：10.1007/s10822-009-9269-0
更新日期：2009-08-01 00:00:00
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journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章
doi：10.1007/BF00124387
更新日期：1992-02-01 00:00:00
abstract：:It is essential, in order to minimise expensive drug failures due to toxicity being found in late development or even in clinical trials, to determine potential toxicity problems as early as possible. In view of the large libraries of compounds now being handled by combinatorial chemistry and high-throughput screening...
journal_title：Journal of computer-aided molecular design
pub_type： 杂志文章,评审
doi：10.1023/a:1025361621494
更新日期：2003-02-01 00:00:00
