Abstract：
:We describe a novel deep learning neural network method and its application to impute assay pIC50 values. Unlike conventional machine learning approaches, this method is trained on sparse bioactivity data as input, typical of that found in public and commercial databases, enabling it to learn directly from correlations between activities measured in different assays. In two case studies on public domain data sets we show that the neural network method outperforms traditional quantitative structure-activity relationship (QSAR) models and other leading approaches. Furthermore, by focusing on only the most confident predictions the accuracy is increased to R2 > 0.9 using our method, as compared to R2 = 0.44 when reporting all predictions.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Whitehead TM,Irwin BWJ,Hunt P,Segall MD,Conduit GJdoi
10.1021/acs.jcim.8b00768subject
Has Abstractpub_date
2019-03-25 00:00:00pages
1197-1204issue
3eissn
1549-9596issn
1549-960Xjournal_volume
59pub_type
杂志文章abstract：:We introduce the statistics behind a novel type of SAR analysis named "nonadditivity analysis". On the basis of all pairs of matched pairs within a given data set, the approach analyzes whether the same transformations between related molecules have the same effect, i.e., whether they are additive. Assuming that the e...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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abstract：:The d-Ala:d-Lac ligase, VanA, plays a critical role in the resistance of vancomycin. Indeed, it is involved in the synthesis of a peptidoglycan precursor, to which vancomycin cannot bind. The reaction catalyzed by VanA requires the opening of the so-called "ω-loop", so that the substrates can enter the active site. He...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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abstract：:The important role of water molecules in protein-ligand binding energetics has attracted wide attention in recent years. A range of computational methods has been developed to predict the favorable locations of water molecules in a protein binding pocket. Most of the current methods are based on extensive molecular dy...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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abstract：:CYP19A1, also known as aromatase or estrogen synthetase, is the rate-limiting enzyme in the biosynthesis of estrogens from their corresponding androgens. Several clinically used breast cancer therapies target aromatase. In this work, explicitly solvated all-atom molecular dynamics simulations of aromatase with a model...
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abstract：:How well do different classification methods perform in selecting the ligands of a protein target out of large compound collections not used to train the model? Support vector machines, random forest, artificial neural networks, k-nearest-neighbor classification with genetic-algorithm-optimized feature selection, tren...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050519k
更新日期：2006-05-01 00:00:00
abstract：:QSPR studies, using scores of SciTegic's extended connectivity fingerprint as raw descriptors, were extended to the prediction of melting points and aqueous solubility of organic compounds. Robust partial least-squares models were developed that perform as well as the best published QSPR models for structurally divers...
journal_title：Journal of chemical information and modeling
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abstract：:Janus kinase 2 (JAK2) is a protein tyrosine kinase implicated in signaling by specific members of the cytokine receptor family. Although it has been established that the JAK2 tyrosine kinase is negatively regulated by the JAK homology 2 (JH2) pseudokinase domain, the underlying mechanism of JH2 mediated regulation rem...
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abstract：:We propose predictive performance criteria for nonlinear regression models without cross-validation. The proposed criteria are the determination coefficient and the root-mean-square error for the midpoints between k-nearest-neighbor data points. These criteria can be used to evaluate predictive ability after the regre...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2013-09-23 00:00:00
abstract：:New molecular descriptors, RED (Renyi entropy descriptors), based on the generalized entropies introduced by Renyi are presented. Topological descriptors based on molecular features have proven to be useful for describing molecular profiles. Renyi entropy is used as a variability measure to contract a feature-pair dis...
journal_title：Journal of chemical information and modeling
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doi：10.1021/ci900275w
更新日期：2009-11-01 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章,评审
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00660
更新日期：2016-04-25 00:00:00
abstract：:It is of great interest in modern drug design to accurately calculate the free energies of protein-ligand or nucleic acid-ligand binding. MM-PBSA (molecular mechanics Poisson-Boltzmann surface area) and MM-GBSA (molecular mechanics generalized Born surface area) have gained popularity in this field. For both methods, ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300064d
更新日期：2012-05-25 00:00:00
abstract：:Class II fructose-1,6-bisphosphate aldolases (FBA-II) are attractive new targets for the discovery of drugs to combat invasive fungal infection, because they are absent in animals and higher plants. Although several FBA-II inhibitors have been reported, none of these inhibitors exhibit antifungal effect so far. In thi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00763
更新日期：2017-06-26 00:00:00
abstract：:Databases of small, potentially bioactive molecules are ubiquitous across the industry and academia. Designed such that each unique compound should appear only once, the multiplicity of ways in which many compounds can be represented means that these databases require methods for standardizing the representation of ch...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00232
更新日期：2020-08-24 00:00:00
abstract：:We present an algorithm, ReFlex3D, for the refinement of flexible molecular alignments based on their three-dimensional shape and electrostatic properties. The algorithm is designed to be used with fast conformer generators to refine an initial overlay between two molecules and thus to obtain improved overlaps as judg...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00618
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700006f
更新日期：2007-07-01 00:00:00
abstract：:Reversible and irreversible covalent ligands are advanced cysteine protease inhibitors in the drug development pipeline. K777 is an irreversible inhibitor of cruzain, a necessary enzyme for the survival of the Trypanosoma cruzi (T. cruzi) parasite, the causative agent of Chagas disease. Despite their importance, irrev...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b01138
更新日期：2020-03-23 00:00:00
abstract：:3-Pyridyl ethers are excellent nAChRs ligands, which show high subtype selectivity and binding affinity to alpha4beta2 nAChR. Although the quantitative structure-activity relationship (QSAR) of nAChRs ligands has been widely investigated using various classes of compounds, the open ring analogues of 3-pyridyl ethers h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0498113
更新日期：2005-03-01 00:00:00
abstract：:The consistent handling of molecules is probably the most basic and important requirement in the field of cheminformatics. Reliable results can only be obtained if the underlying calculations are independent of the specific way molecules are represented in the input data. However, ensuring consistency is a complex tas...
journal_title：Journal of chemical information and modeling
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doi：10.1021/ci400724v
更新日期：2014-03-24 00:00:00
abstract：:Umami or the taste of monosodium glutamate represents one of the major attractive taste modalities in humans. Therefore, knowledge about biophysical and biochemical properties of the umami taste is important for both scientific research and the food industry. Experimental approaches for predicting umami peptides are l...
journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
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abstract：:Inhibition of plasmin has been found to effectively reduce fibrinolysis and to avoid hemorrhage. This can be achieved by addressing its kringle 1 domain with the known drug and lysine analogue tranexamic acid. Guided by shape similarities toward a previously discovered lead compound, 5-(4-piperidyl)isoxazol-3-ol, a se...
journal_title：Journal of chemical information and modeling
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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 a...
journal_title：Journal of chemical information and modeling
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abstract：:Molecular docking can account for receptor flexibility by combining the docking score over multiple rigid receptor conformations, such as snapshots from a molecular dynamics simulation. Here, we evaluate a number of common snapshot selection strategies using a quality metric from stratified sampling, the efficiency of...
journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
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abstract：:The purpose of this investigation is to contribute to the development of new anticonvulsant drugs to treat patients with refractory epilepsy. We applied a virtual screening protocol that involved the search into molecular databases of new compounds and known drugs to find small molecules that interact with the open co...
journal_title：Journal of chemical information and modeling
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abstract：:Three-dimensional protein structures are a key requisite for structure-based drug discovery. For many highly relevant targets, medicinal chemists are confronted with large numbers of target structures in their apo-forms or in complex with a wealth of different ligands. To exploit the full potential of such structure e...
journal_title：Journal of chemical information and modeling
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