Abstract:
:The modeling of nonlinear descriptor-target relationships is a topic of considerable interest in drug discovery. We, herein, continue reporting the use of the self-organizing map-a nonlinear, topology-preserving pattern recognition technique that exhibits considerable promise in modeling and decoding these relationships. Since simulated annealing is an efficient tool for solving optimization problems, we combined the supervised self-organizing map with simulated annealing to build high-quality, highly predictive quantitative structure-activity/property relationship models. This technique was applied to six data sets representing a variety of biological endpoints. Since a high statistical correlation in the training set does not indicate a highly predictive model, the quality of all the models was confirmed by withholding a portion of each data set for external validation. Finally, we introduce new cross-validation and dynamic partitioning techniques to address model overfitting and assessment.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Xiao YD,Harris R,Bayram E,Ii PS,Schmitt JDdoi
10.1021/ci0500841keywords:
subject
Has Abstractpub_date
2006-01-01 00:00:00pages
137-44issue
1eissn
1549-9596issn
1549-960Xjournal_volume
46pub_type
杂志文章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::The cannabinoid receptor subtype 2 (CB2) is a promising therapeutic target for blood cancer, pain relief, osteoporosis, and immune system disease. The recent withdrawal of Rimonabant, which targets another closely related cannabinoid receptor (CB1), accentuates the importance of selectivity for the development of CB2 ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci3003914
更新日期:2013-01-28 00:00:00
abstract::In this study, we aimed to develop a new ligand-based virtual screening approach using an effective shape-overlapping procedure and a more robust scoring function (denoted by the HWZ score for convenience). The HWZ score-based virtual screening approach was tested against the compounds for 40 protein targets available...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200617d
更新日期:2012-04-23 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::Machine learning has exhibited powerful capabilities in many areas. However, machine learning models are mostly database dependent, requiring a new model if the database changes. Therefore, a universal model is highly desired to accommodate the widest variety of databases. Fortunately, this universality may be achieve...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00878
更新日期:2019-05-28 00:00:00
abstract::Reversible covalent inhibitors have drawn increasing attention in drug design, as they are likely more potent than noncovalent inhibitors and less toxic than covalent inhibitors. Despite those advantages, the computational prediction of reversible covalent binding presents a formidable challenge because the binding pr...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00959
更新日期:2019-05-28 00:00:00
abstract::The molecular structure of four dimeric units (D-E, E-F, F-G, and G-H) of the DEFGH structural unit of heparin, their anionic forms, and their sodium salts have been studied using the B3LYP/6-31+G(d) method. The optimized geometries indicate that the most stable structure of these dimeric units in neutral state is sta...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci060060+
更新日期:2006-07-01 00:00:00
abstract::The current drug virtual screen (VS) methods mainly include two categories. i.e., ligand/target structure-based virtual screen and that, utilizing protein-ligand interaction fingerprint information based on the large number of complex structures. Since the former one focuses on the one-side information while the later...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200481c
更新日期:2012-03-26 00:00:00
abstract::We have developed a computer program for molecular dynamics (MD) simulation that implements the Split Integration Symplectic Method (SISM) and is designed to run on specialized parallel computers. The MD integration is performed by the SISM, which analytically treats high-frequency vibrational motion and thus enables ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050216q
更新日期:2005-11-01 00:00:00
abstract::Human type II topoisomerases, molecular motors that alter the DNA topology, are a major target of modern chemotherapy. Groups of catalytic inhibitors represent a new approach to overcome the known limitations of topoisomerase II poisons such as cardiotoxicity and induction of secondary tumors. Here, we present a class...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00202
更新日期:2020-07-27 00:00:00
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
pub_type: 杂志文章
doi:10.1021/ci060093p
更新日期:2006-09-01 00:00:00
abstract::Taking into account dynamical behavior and/or structural inaccuracies of receptor-ligand systems becomes increasingly important in structure-based drug design. Here, we describe the development of consensus Adaptation of Fields for Molecular Comparison (AFMoC) (abbreviated as AFMoCcon) models that account for multiple...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci7002472
更新日期:2007-11-01 00:00:00
abstract::Arachidonic acid is an essential fatty acid in cells, acting as a key inflammatory intermediate in inflammatory reactions. In cardiac tissues, CYP2J2 can adopt arachidonic acid as a major substrate to produce epoxyeicosatrienoic acids (EETs), which can protect endothelial cells from ischemic or hypoxic injuries and ha...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400003p
更新日期:2013-06-24 00:00:00
abstract::The protonation states for nucleic acid bases are difficult to assess experimentally. In the context of DNA triplex, the protonation state of cytidine in the third strand is particularly important, because it needs to be protonated in order to form Hoogsteen hydrogen bonds. A sugar modification, locked nucleic acid (L...
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::Following the theoretical model by Hann et al. moderately complex structures are preferable lead compounds since they lead to specific binding events involving the complete ligand molecule. To make this concept usable in practice for library design, we studied several complexity measures on the biological activity of ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0503558
更新日期:2006-03-01 00:00:00
abstract::A machine learning enhanced spectrum recognition system called spectrum recognition based on computer vision (SRCV) for data extraction from previously analyzed 13C and 1H NMR spectra has been developed. The intelligent system was designed with four function modules to extract data from three areas of NMR images, incl...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c01046
更新日期:2021-01-25 00:00:00
abstract::Our main objective was to compile a data set of high-quality protein-fragment complexes and make it publicly available. Once assembled, the data set was challenged using docking procedures to address the following questions: (i) Can molecular docking correctly reproduce the experimentally solved structures? (ii) How t...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci2003363
更新日期:2011-11-28 00:00:00
abstract::Resonance structures of polycyclic aromatic hydrocarbons can be associated with numerical formulas by assigning pi-electrons of C=C double bonds to individual benzenoid rings. Each C=C double bond in a resonance structure assigns two pi-electrons to a ring in a fused-benzenoid system if it is not shared by adjacent ri...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050196s
更新日期:2006-01-01 00:00:00
abstract::We present an induced fit docking approach called Adaptive BP-Dock that integrates perturbation response scanning (PRS) with the flexible docking protocol of RosettaLigand in an adaptive manner. We first perturb the binding pocket residues of a receptor and obtain a new conformation based on the residue response fluct...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00587
更新日期:2016-04-25 00:00:00
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
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00051
更新日期:2020-04-27 00:00:00
abstract::As a result of the widespread industrial use of polychlorinated hydrocarbons, they have accumulated in nearly all types of environmental compartments, especially in aquatic systems. Particularly, chloroaromatics are among the most undesirable industrial effluents because of their persistence and toxicity. To predict c...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0501342
更新日期:2005-07-01 00:00:00
abstract::The partitioning of solute molecules between immiscible solvents with significantly different polarities is of great importance. The polarization between the solute and solvent molecules plays an essential role in determining the solubility of the solute, which makes computational studies utilizing molecular mechanics...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00001
更新日期:2017-10-23 00:00:00
abstract::Activity cliffs are formed by structurally similar compounds having large potency differences. Coordinated activity cliffs evolve when compounds within groups of structural neighbors form multiple cliffs with different partners, giving rise to local networks of cliffs in a data set. Using particle swarm optimization, ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci3000503
更新日期:2012-04-23 00:00:00
abstract::Determination of structural similarities between protein binding pockets is an important challenge in in silico drug design. It can help to understand selectivity considerations, predict unexpected ligand cross-reactivity, and support the putative annotation of function to orphan proteins. To this end, Cavbase was dev...
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 proton conduction of transmembrane influenza virus B M2 (BM2) proton channel is possibly mediated by the membrane environment, but the detailed molecular mechanism is challenging to determine. In this work, how membrane lipid composition regulates the conformation and hydration of BM2 channel is elucidated in sili...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00329
更新日期:2020-07-27 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::In this study, we have developed a two model system to mimic the active and inactive states of a G-protein coupled receptor specifically the alpha1A adrenergic receptor. We have docked two agonists, epinephrine (phenylamine type) and oxymetazoline (imidazoline type), as well as two antagonists, prazosin and 5-methylur...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700026v
更新日期:2007-09-01 00:00:00
abstract::We investigate unexpectedly short non-covalent distances (<85% of the sum of van der Waals radii) in X-ray crystal structures of proteins. We curate over 11 000 high-quality protein crystal structures and an ultra-high-resolution (1.2 Å or better) subset containing >900 structures. Although our non-covalent distance c...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00144
更新日期:2019-05-28 00:00:00
abstract::Congeners are molecules based on the same carbon skeleton but are different by the number of substituents and/or a substitution pattern. Examples are 1-chloronaphthalene, 1,4-dichloronaphthalene, and 1,3,8-trichloronaphthalene. Various persistent organic pollutants (POPs) exist in the environment as families of congen...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300289b
更新日期:2012-11-26 00:00:00
abstract::Virtual screening is routinely used to discover new ligands and in particular new ligand chemotypes for G protein-coupled receptors (GPCRs). To prepare for a virtual screen, we often tailor a docking protocol that will enable us to select the best candidates for further screening. To aid this, we created GPCR-Bench, a...
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