Abstract:
:Computer-aided drug design could benefit from a greater understanding of how errors arise and propagate in biomolecular modeling. With such knowledge, model predictions could be associated with quantitative estimates of their uncertainty. In addition, novel algorithms could be designed to proactively reduce prediction errors. We investigated how errors propagate in statistical mechanical ensembles and found that free energy evaluations based on single molecular configurations yield maximum uncertainties in free energy. Furthermore, increasing the size of the ensemble by sampling and averaging over additional independent configurations reduces uncertainties in free energy dramatically. This finding suggests a general strategy that could be utilized as a post-hoc correction for improved precision in virtual screening and free energy estimation.
journal_name
ACS Med Chem Lettjournal_title
ACS medicinal chemistry lettersauthors
Faver JC,Ucisik MN,Yang W,Merz KM Jrdoi
10.1021/ml4002634subject
Has Abstractpub_date
2013-09-12 00:00:00issue
9issn
1948-5875journal_volume
4pub_type
杂志文章abstract::Self-repair of nuclear DNA damage is the most known reason that leads to drug resistance of cancer tissue and limited therapeutic efficacy of anticancer drugs. Inhibition of protein phosphatase 2A (PP2A) would block DNA damage-induced defense of cancer cells to suppress DNA repair for enhanced cancer treatment. Here, ...
journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
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journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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更新日期:2013-10-01 00:00:00
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
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pub_type: 杂志文章
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journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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journal_title:ACS medicinal chemistry letters
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pub_type: 杂志文章
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更新日期:2014-08-19 00:00:00
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journal_title:ACS medicinal chemistry letters
pub_type: 社论
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journal_title:ACS medicinal chemistry letters
pub_type: 社论
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journal_title:ACS medicinal chemistry letters
pub_type: 杂志文章
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