Abstract：
:Whereas 400 million distinct compounds are now purchasable within the span of a few weeks, the biological activities of most are unknown. To facilitate access to new chemistry for biology, we have combined the Similarity Ensemble Approach (SEA) with the maximum Tanimoto similarity to the nearest bioactive to predict activity for every commercially available molecule in ZINC. This method, which we label SEA+TC, outperforms both SEA and a naïve-Bayesian classifier via predictive performance on a 5-fold cross-validation of ChEMBL's bioactivity data set (version 21). Using this method, predictions for over 40% of compounds (>160 million) have either high significance (pSEA ≥ 40), high similarity (ECFP4MaxTc ≥ 0.4), or both, for one or more of 1382 targets well described by ligands in the literature. Using a further 1347 less-well-described targets, we predict activities for an additional 11 million compounds. To gauge whether these predictions are sensible, we investigate 75 predictions for 50 drugs lacking a binding affinity annotation in ChEMBL. The 535 million predictions for over 171 million compounds at 2629 targets are linked to purchasing information and evidence to support each prediction and are freely available via https://zinc15.docking.org and https://files.docking.org .
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Irwin JJ,Gaskins G,Sterling T,Mysinger MM,Keiser MJdoi
10.1021/acs.jcim.7b00316subject
Has Abstractpub_date
2018-01-22 00:00:00pages
148-164issue
1eissn
1549-9596issn
1549-960Xjournal_volume
58pub_type
杂志文章abstract：:We propose an improved solvent contact model to estimate the solvation free energy of an organic molecule from individual atomic contributions. The modification of the solvation model involves the optimization of three kinds of parameters in the solvation free energy function: atomic fragmental volume, maximum atomic ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600453b
更新日期：2007-03-01 00:00:00
abstract：:In this work, we present molecular modeling studies carried out using six DNA sequences and six azinomycin analogues, including the naturally occurring compound azinomycin B, selected on the basis of known cell cytotoxicity and structural analogies (epoxide and aziridine alkylating moieties). Among several computation...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0496595
更新日期：2005-05-01 00:00:00
abstract：:Optimization of ligand binding affinity to the target protein of interest is a primary objective in small-molecule drug discovery. Until now, the prediction of binding affinities by computational methods has not been widely applied in the drug discovery process, mainly because of its lack of accuracy and reproducibili...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00780
更新日期：2017-04-24 00:00:00
abstract：:Resistance remains a major issue with regards to HIV-1 protease, despite the availability of numerous HIV-1 protease inhibitors and copious amounts of structural and binding data. In an effort to improve our understanding of how HIV-1 protease is able to "outsmart" new drugs, we have investigated the flexibility of HI...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci2000677
更新日期：2011-05-23 00:00:00
abstract：:Most drugs exert their effects via multitarget interactions, as hypothesized by polypharmacology. While these multitarget interactions are responsible for the clinical effect profiles of drugs, current methods have failed to uncover the complex relationships between them. Here, we introduce an approach which is able t...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci2002022
更新日期：2012-01-23 00:00:00
abstract：:DNA damage alters genetic information and adversely affects gene expression pathways leading to various complex genetic disorders and cancers. DNA repair proteins recognize and rectify DNA damage and mismatches with high fidelity. A critical molecular event that occurs during most protein-mediated DNA repair processes...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00636
更新日期：2018-03-26 00:00:00
abstract：:In the preceding paper (Duca, J. S.; Madison, V. S.; Voigt, J. H. J. Chem. Inf. Model. 2008, 48, 659-668), the accuracy of docking and affinity predictions of the Gold and Glide programs were investigated using single protein conformations spanning 150 CDK2/inhibitor crystallographic complexes. High docking accuracy w...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700428d
更新日期：2008-03-01 00:00:00
abstract：:The in silico prediction of unwanted side effects (SEs) caused by the promiscuous behavior of drugs and their targets is highly relevant to the pharmaceutical industry. Considerable effort is now being put into computational and experimental screening of several suspected off-target proteins in the hope that SEs might...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00120
更新日期：2015-09-28 00:00:00
abstract：:Traditional herbal medicine has been an inseparable part of the traditional medical science in many countries throughout history. Nowadays, the popularity of using herbal medicines in daily life, as well as clinical practices, has gradually expanded to numerous Western countries with positive impacts and acceptance. T...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00826
更新日期：2020-03-23 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00400
更新日期：2016-12-27 00:00:00
abstract：:Carcinogenicity is an important toxicological endpoint that poses high concern to drug discovery. In this study, we developed a method to extract structural alerts (SAs) and modulating factors of carcinogens on the basis of statistical analyses. First, the Gaston algorithm, a frequent subgraph mining method, was used ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300266p
更新日期：2012-08-27 00:00:00
abstract：:A database of about 700 high-resolution kinase structures was used to test the reliability of 17 docking procedures (using six docking software packages) by means of self- and cross-docking studies. The analysis of about 80 000 docking calculations suggests that the docking of an unknown ligand into a kinase has a pro...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100161z
更新日期：2010-08-23 00:00:00
abstract：:A kinetic, reactivity-binding model has been proposed to predict the regioselectivity of substrates meditated by the CYP1A2 enzyme, which is responsible for the metabolism of planar-conjugated compounds such as caffeine. This model consists of a docking simulation for binding energy and a semiempirical molecular orbit...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800001m
更新日期：2008-05-01 00:00:00
abstract：:The α2a adrenoceptor is a medically relevant subtype of the G protein-coupled receptor family. Unfortunately, high-throughput techniques aimed at producing novel drug leads for this receptor have been largely unsuccessful because of the complex pharmacology of adrenergic receptors. As such, cutting-edge in silico liga...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c01019
更新日期：2021-01-25 00:00:00
abstract：:Dual and triple activity-difference (DAD/TAD) maps are tools for the systematic characterization of structure-activity relationships (SAR) of compound data sets screened against two or three targets. DAD and TAD maps are two- and three- dimensional representations of the pairwise activity differences of compound data ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200281v
更新日期：2011-09-26 00:00:00
abstract：:Piperine, the bioactive phytochemical from black pepper (Piper nigrum L.), is a nontoxic natural compound exhibiting many physiological and pharmacological properties. They include antioxidant, anti-inflammatory, antimutagenic, antitumor, antiapoptotic, antigenotoxic, antiarthritic, antifungal, antimicrobial, antidepr...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00514
更新日期：2015-12-28 00:00:00
abstract：:Estrogens exert important physiological effects through the modulation of two human estrogen receptor (hER) subtypes, alpha (hERalpha) and beta (hERbeta). Because the levels and relative proportion of hERalpha and hERbeta differ significantly in different target cells, selective hER ligands could target specific tissu...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci8002182
更新日期：2008-11-01 00:00:00
abstract：:The primary goal of ligand-based virtual screening is to identify active compounds consisting of a core scaffold that is not found in the current active compound pool. Scaffold hopping is the term used for this purpose. In the present study, topological representations of pharmacophore features on chemical graphs were...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00098
更新日期：2020-04-27 00:00:00
abstract：:Simulating protein flexibility is a major issue in the docking-based drug-design process for which a single methodological solution does not exist. In our search of new anti-Alzheimer ligands, we were faced with the challenge of including receptor plasticity in a virtual screening campaign aimed at finding new β-secre...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300390h
更新日期：2012-10-22 00:00:00
abstract：:Antimicrobial peptides (AMPs) have emerged as promising therapeutic alternatives to fight against the diverse infections caused by different pathogenic microorganisms. In this context, theoretical approaches in bioinformatics have paved the way toward the creation of several in silico models capable of predicting anti...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00630
更新日期：2016-03-28 00:00:00
abstract：:Large corpora of kinase small molecule inhibitor data are accessible to public sector research from thousands of journal article and patent publications. These data have been generated employing a wide variety of assay methodologies and experimental procedures by numerous laboratories. Here we ask the question how app...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300403k
更新日期：2013-01-28 00:00:00
abstract：:Molecular docking programs are widely used modeling tools for predicting ligand binding modes and structure based virtual screening. In this study, six molecular docking programs (DOCK, FlexX, GLIDE, ICM, PhDOCK, and Surflex) were evaluated using metrics intended to assess docking pose and virtual screening accuracy. ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900056c
更新日期：2009-06-01 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5005898
更新日期：2015-01-26 00:00:00
abstract：:The human DNA-repair O (6)-alkylguanine DNA alkyltransferase (MGMT or hAGT) protein protects DNA from environmental alkylating agents and also plays an important role in tumor resistance to chemotherapy treatment. Available inhibitors, based on pseudosubstrate analogs, have been shown to induce substantial bone marrow...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700447r
更新日期：2008-04-01 00:00:00
abstract：:Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction. However, sildenafil causes side effects on visual functions since it shows similar potencies to inhibit PDE5 and PDE6, whereas tadalaf...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400458z
更新日期：2013-11-25 00:00:00
abstract：:Ab initio quantum-chemistry programs produce and use large amounts of data, which are usually stored on disk in the form of binary files. A FORTRAN library, named Q5Cost, has been designed and implemented in order to allow the storage of these data sets in a special data format built with the HDF5 technology. This dat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci7000567
更新日期：2007-05-01 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200078f
更新日期：2011-09-26 00:00:00
abstract：:An important issue in developing protein-ligand docking methods is how to incorporate receptor flexibility. Consideration of receptor flexibility using an ensemble of precompiled receptor conformations or by employing an effectively enlarged binding pocket has been reported to be useful. However, direct consideration ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300342z
更新日期：2012-12-21 00:00:00
abstract：:SMIfp (SMILES fingerprint) is defined here as a scalar fingerprint describing organic molecules by counting the occurrences of 34 different symbols in their SMILES strings, which creates a 34-dimensional chemical space. Ligand-based virtual screening using the city-block distance CBD(SMIfp) as similarity measure provi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400206h
更新日期：2013-08-26 00:00:00
abstract：:The Torsion Library contains hundreds of rules for small molecule conformations which have been derived from the Cambridge Structural Database (CSD) and are curated by molecular design experts. The torsion rules are encoded as SMARTS patterns and categorize rotatable bonds via a traffic light coloring scheme. We have ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00522
更新日期：2016-01-25 00:00:00
