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, trend vectors, naïve Bayesian classification, and decision tree were used to divide databases into molecules predicted to be active and those predicted to be inactive. Training and predicted activities were treated as binary. The database was generated for the ligands of five different biological targets which have been the object of intense drug discovery efforts: HIV-reverse transcriptase, COX2, dihydrofolate reductase, estrogen receptor, and thrombin. We report significant differences in the performance of the methods independent of the biological target and compound class. Different methods can have different applications; some provide particularly high enrichment, others are strong in retrieving the maximum number of actives. We also show that these methods do surprisingly well in predicting recently published ligands of a target on the basis of initial leads and that a combination of the results of different methods in certain cases can improve results compared to the most consistent method.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Plewczynski D,Spieser SA,Koch Udoi
10.1021/ci050519ksubject
Has Abstractpub_date
2006-05-01 00:00:00pages
1098-106issue
3eissn
1549-9596issn
1549-960Xjournal_volume
46pub_type
杂志文章abstract：:Molecular fragment dynamics (MFD) is a variant of dissipative particle dynamics (DPD), a coarse-grained mesoscopic simulation technique for isothermal complex fuids and soft matter systems with particles that are chosen to be adequate fluid elements. MFD choses its particles to be small molecules which may be connecte...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5006096
更新日期：2015-05-26 00:00:00
abstract：:The possibility of improving the predictive ability of comparative molecular field analysis (CoMFA) by settings optimization has been evaluated to show that CoMFA predictive ability can be improved. Ten different CoMFA settings are evaluated, producing a total of 6120 models. This method has been applied to nine diffe...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci049612j
更新日期：2006-01-01 00:00:00
abstract：:Deep learning has drawn significant attention in different areas including drug discovery. It has been proposed that it could outperform other machine learning algorithms, especially with big data sets. In the field of pharmaceutical industry, machine learning models are built to understand quantitative structure-acti...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00671
更新日期：2019-03-25 00:00:00
abstract：:Mapping the chemical space of small organic molecules is approached from a theoretical graph theory viewpoint, in an effort to begin the systematic exploration of molecular topologies. We present an algorithm for exhaustive generation of scaffold topologies with up to eight rings and an efficient comparison method for...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci7003412
更新日期：2008-07-01 00:00:00
abstract：:Advances in the development of high-throughput screening and automated chemistry have rapidly accelerated the production of chemical and biological data, much of them freely accessible through literature aggregator services such as ChEMBL and PubChem. Here, we explore how to use this comprehensive mapping of chemical ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00526
更新日期：2019-11-25 00:00:00
abstract：:Metabolism of xenobiotic and endogenous compounds is frequently complex, not completely elucidated, and therefore often ambiguous. The prediction of sites of metabolism (SoM) can be particularly helpful as a first step toward the identification of metabolites, a process especially relevant to drug discovery. This pape...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400058s
更新日期：2013-06-24 00:00:00
abstract：:As computational drug design becomes increasingly reliant on virtual screening and on high-throughput 3D modeling, the need for fast, robust, and reliable methods for sampling molecular conformations has become greater than ever. Furthermore, chemical novelty is at a premium, forcing medicinal chemists to explore more...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900238a
更新日期：2009-10-01 00:00:00
abstract：:Identifying drug-target interactions (DTIs) plays an important role in the field of drug discovery, drug side-effects, and drug repositioning. However, in vivo or biochemical experimental methods for identifying new DTIs are extremely expensive and time-consuming. Recently, in silico or various computational methods h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00408
更新日期：2019-07-22 00:00:00
abstract：:In the present work, the Henderson-Hasselbalch (HH) equation has been employed for the development of a tool for the prediction of pH-dependent aqueous solubility of drugs and drug candidates. A new prediction method for the intrinsic solubility was developed, based on artificial neural networks that have been trained...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600292q
更新日期：2006-11-01 00:00:00
abstract：:An accurate scoring function is expected to correctly select the most stable structure from a set of pose candidates. One can hypothesize that a scoring function's ability to identify the most stable structure might be improved by emphasizing the most relevant atom pairwise interactions. However, it is hard to evaluat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00356
更新日期：2019-07-22 00:00:00
abstract：:There is a renewed interest in computer-aided synthesis planning, where the vast majority of approaches require the application of retrosynthetic reaction templates. Here we introduce RDChiral, an open-source Python wrapper for RDKit designed to provide consistent handling of stereochemical information in applying ret...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00286
更新日期：2019-06-24 00:00:00
abstract：:Ergotamine (ERG) and dihydroergotamine (DHE), common migraine drugs, have small structural differences but lead to clinically important distinctions in their pharmacological profiles. For example, DHE is less potent than ERG by about 10-fold at the 5-hydroxytrptamine receptor 1B (5-HT1B). Although the high-resolution ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b01082
更新日期：2020-03-23 00:00:00
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
doi：10.1021/ci4003766
更新日期：2013-09-23 00:00:00
abstract：:The viral NS5B RNA-dependent RNA-polymerase (RdRp) is one of the best-studied and promising targets for the development of novel therapeutics against hepatitis C virus (HCV). Allosteric inhibition of this enzyme has emerged as a viable strategy toward blocking replication of viral RNA in cell based systems. Herein, we...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9004749
更新日期：2010-04-26 00:00:00
abstract：:Distribution patterns of 8411 compounds from 240 Chinese herbs were analyzed in relation to the herbal categories of traditional Chinese medicine (TCM), using Random Forest (RF) and self-organizing maps (SOM). RF was used first to construct TCM profiles of individual compounds, which describe their affinities for 28 m...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700155t
更新日期：2007-11-01 00:00:00
abstract：:Factor Xa inhibitors are innovative anticoagulant agents that provide a better safety/efficacy profile compared to other anticoagulative drugs. A chemical feature-based modeling approach was applied to identify crucial pharmacophore patterns from 3D crystal structures of inhibitors bound to human factor Xa (Pdb entrie...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci049778k
更新日期：2005-01-01 00:00:00
abstract：:Curvularia lunata is a dark pigmented fungus that is the causative agent of several diseases in plants and in both immunodeficient and immunocompetent patients. 1,8-Dihydroxynaphthalene-melanin is found in the cell wall of C. lunata and is believed to be the important virulence factor of dematiaceous fungi. Trihydroxy...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci2001499
更新日期：2011-07-25 00:00:00
abstract：:Artificial intelligence and multiobjective optimization represent promising solutions to bridge chemical and biological landscapes by addressing the automated de novo design of compounds as a result of a humanlike creative process. In the present study, we conceived a novel pair-based multiobjective approach implement...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00517
更新日期：2020-10-26 00:00:00
abstract：:Encapsulation of peptide and protein-based drugs in polymeric nanoparticles is one of the fundamental fields in controlled-release drug delivery systems. The molecular mechanisms of absorption of peptides to the polymeric nanoparticles are still unknown, and there is no precise molecular data on the encapsulation proc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00641
更新日期：2019-01-28 00:00:00
abstract：:Chemical structure extraction from documents remains a hard problem because of both false positive identification of structures during segmentation and errors in the predicted structures. Current approaches rely on handcrafted rules and subroutines that perform reasonably well generally but still routinely encounter s...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00669
更新日期：2019-03-25 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：:Herein we present the VMD Store, an open-source VMD plugin that simplifies the way that users browse, discover, install, update, and uninstall extensions for the Visual Molecular Dynamics (VMD) software. The VMD Store obtains data about all the indexed VMD extensions hosted on GitHub and presents a one-click mechanism...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00739
更新日期：2019-11-25 00:00:00
abstract：:Reduction of the affinity of the fragment crystallizable (Fc) region with immune receptors by substitution of one or a few amino acids, known as Fc-silencing, is an established approach to reduce the immune effector functions of monoclonal antibody therapeutics. This approach to Fc-silencing, however, is problematic a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b01198
更新日期：2020-11-23 00:00:00
abstract：:Predictive metabolism methods can be used in drug discovery projects to enhance the understanding of structure-metabolism relationships. The present study uses data mining methods to exploit biotransformation data that have been recorded in the MDL Metabolite database. Reacting center fingerprints were derived from a ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600376q
更新日期：2007-03-01 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：:In this study, in order to elucidate the action mechanism of traditional Chinese medicines (TCMs) that exhibit clinical efficacy for type II diabetes mellitus (T2DM), an integrated protocol that combines molecular docking and pharmacophore mapping was employed to find the potential inhibitors from TCM for the T2DM-rel...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400146u
更新日期：2013-07-22 00:00:00
abstract：:Human cannabinoid type 1 (CB1) G-protein coupled receptor is a potential therapeutic target for obesity. The previously predicted and experimentally validated ensemble of ligand-free conformations of CB1 [Scott, C. E. et al. Protein Sci. 2013 , 22 , 101 - 113 ; Ahn, K. H. et al. Proteins 2013 , 81 , 1304 - 1317] are u...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00581
更新日期：2016-01-25 00:00:00
abstract：:Molecular dynamics simulations provide valuable insights into the behavior of molecular systems. Extending the recent trend of using machine learning techniques to predict physicochemical properties from molecular dynamics data, we propose to consider the trajectories as multidimensional time series represented by 2D ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00135
更新日期：2019-08-26 00:00:00
abstract：:Different forms of synaptic plasticity in the cerebellum expressed at the synapses onto Purkinje cells (PCs) are mediated by membrane metabotropic glutamate receptors (mGluRs). There are three main mGluR groups with a total of 8 subtypes. Although mGluRs are also found at the climbing fiber (CF) to PC synapses, the di...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050161s
更新日期：2005-11-01 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
