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：:The large volume of protein-ligand structures now available enables innovative and efficient protocols in computational FBDD (Fragment-Based Drug Design) to be proposed based on experimental data. In this work, we build a database of MED-Portions, where a MED-Portion is a new structural object encoding protein-fragmen...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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abstract：:A theoretical study of a variety of cyclohexane-based anion transporters interacting with the chloride anion has been conducted using density functional theory. The calculations have been performed in the gas phase but also, in order to describe the solvation effects on the interaction, two different solvents-chlorofo...
journal_title：Journal of chemical information and modeling
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abstract：:To discover non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) that are effective against both wild-type (WT) virus and variants that encode the clinically troublesome Tyr181Cys (Y181C) RT mutation, virtual screening by docking was carried out using three RT structures and more than 2 million commercial...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900068k
更新日期：2009-05-01 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
pub_type： 杂志文章
doi：10.1021/ci900275w
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abstract：:Covalent inhibitors have been gaining increased attention in drug discovery due to their beneficial properties such as long residence time, high biochemical efficiency, and specificity. Optimization of covalent inhibitors is a complex task that involves parallel monitoring of the noncovalent recognition elements and t...
journal_title：Journal of chemical information and modeling
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doi：10.1021/acs.jcim.0c00834
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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
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journal_title：Journal of chemical information and modeling
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00083
更新日期：2016-06-27 00:00:00
abstract：:Nonalcoholic hepatic steatosis is a worldwide epidemiological concern since it is among the most prominent hepatic diseases. Indeed, research in toxicology and epidemiology has gathered evidence that exposure to endocrine disruptors can perturb cellular homeostasis and cause this disease. Therefore, assessing the like...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00297
更新日期：2018-08-27 00:00:00
abstract：:The accurate prediction of the adsorption energies of unsaturated molecules on graphene in the presence of water is essential for the design of molecules that can modify its properties and that can aid its processability. We here show that a semiempirical MO method corrected for dispersive interactions (PM6-DH2) can p...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5003729
更新日期：2014-08-25 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.0c00201
更新日期：2020-10-26 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.9b00132
更新日期：2019-09-23 00:00:00
abstract：:Support vector regression (SVR) is a premier approach for the prediction of compound potency. Given the conceptual link between support vector machine (SVM) and SVR modeling, SVR is capable of accounting for continuous and discontinuous structure-activity relationships (SARs) in potency prediction, which further exten...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00584
更新日期：2019-03-25 00:00:00
abstract：:Structure-based virtual screening is highly used in the early stages of drug discovery to identify new putative lead compounds for a given target. However, when a small molecule elicits a biological effect, but its target is unknown, or the side effects it causes arise from its undesired interaction with unknown count...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00428
更新日期：2019-11-25 00:00:00
abstract：:The primary goal of this project was to evaluate the performance of the Standard and Enforced Geometry Optimization (SEGO) method which we have recently developed. The SEGO method has been designed for an automatic location of multiple minima on the molecular Potential Energy Surface (PES), and its usefulness has been...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00352
更新日期：2019-08-26 00:00:00
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journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100099g
更新日期：2010-09-27 00:00:00
abstract：:Voltage-gated sodium channels (VGSC) are attractive targets for drug discovery because of the broad therapeutic potential of their modulators. On the basis of the structure of marine alkaloid clathrodin, we have recently discovered novel subtype-selective VGSC modulators I and II that were used as starting points for ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400505e
更新日期：2013-12-23 00:00:00
abstract：:Solute-solvent interactions are critical for biomolecular stability and recognition. Explicit solvent molecular dynamics (MD) simulations are routinely used to probe such interactions. However, detailed analyses and interpretation of the hydration patterns seen in MD simulations can be both complex and time-consuming....
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00453
更新日期：2019-07-22 00:00:00
abstract：:In this work, we present a systematical investigation of the influence of ligand protonation states, stereoisomers, and tautomers on results obtained with the two protein-ligand docking programs GOLD and PLANTS. These different states were generated with a fully automated tool, called SPORES (Structure PrOtonation and...
journal_title：Journal of chemical information and modeling
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doi：10.1021/ci800420z
更新日期：2009-06-01 00:00:00
abstract：:Using an all-atom explicit water model and replica exchange umbrella sampling simulations, we investigated the molecular mechanisms of benzoic acid partitioning into two model lipid bilayers. The first was formed of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipids, whereas the second was composed of an equimo...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00590
更新日期：2020-08-24 00:00:00
abstract：:Discovery of new antibacterial agents is a never-ending task of medicinal chemistry. Every new drug brings significant improvement to patients with bacterial infections, but prolonged usage of antibacterials leads to the emergence of resistant strains. Therefore, novel active structures with new modes of action are re...
journal_title：Journal of chemical information and modeling
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doi：10.1021/acs.jcim.9b00436
更新日期：2019-11-25 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.7b00741
更新日期：2018-04-23 00:00:00
abstract：:Flavonoids, the vastest class of natural polyphenols, are extensively investigated for their multiple benefits on human health. Due to their physicochemical or biological properties, many representatives are considered to exhibit low selectivity among various protein targets or to plague high-throughput screening (HTS...
journal_title：Journal of chemical information and modeling
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doi：10.1021/ci5002668
更新日期：2014-08-25 00:00:00
abstract：:Protein-protein interactions are central to many biological processes, from intracellular communication to cytoskeleton assembly, and therefore represent an important class of targets for new therapeutics. The most common secondary structure in natural proteins is an α-helix. Small molecules seem to be attractive cand...
journal_title：Journal of chemical information and modeling
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更新日期：2012-02-27 00:00:00
abstract：:Protein-polysaccharide complexes constructed via self-assembly methods are often used to develop novel biomaterials for a wide range of applications in biomedicine, food, and biotechnology. The objective of this work was to investigate theoretically and to demonstrate via constant-pH Monte Carlo simulations that the c...
journal_title：Journal of chemical information and modeling
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更新日期：2020-02-24 00:00:00
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journal_title：Journal of chemical information and modeling
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abstract：:Cathepsin A is a mammalian lysosomal enzyme that catalyzes the hydrolysis of the carboxy-terminal amino acids of polypeptides and also regulates beta-galactosidase and neuraminidase-1 activities through the formation of a multienzymic complex in lysosomes. Human cathepsin A (hCathA), yeast carboxypeptidase (CPY), and ...
journal_title：Journal of chemical information and modeling
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更新日期：2006-09-01 00:00:00
abstract：:The human cytochrome P450 (CYP450) isozymes are the most important enzymes in the body to metabolize many endogenous and exogenous substances including environmental toxins and therapeutic drugs. Any unnecessary interactions between a small molecule and CYP450 isozymes may raise a potential to disarm the integrity 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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更新日期：2020-10-26 00:00:00
abstract：:Aminoglycosides are antibiotics targeting the 16S RNA A site of the bacterial ribosome. There have been many efforts directed toward design of their synthetic derivatives, however with only few successes. As RNA binders, aminoglycosides are also a difficult target for computational drug design, since most of the exist...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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