Abstract：
:Porcupine is a component of the Wnt pathway which regulates cell proliferation, migration, stem cell self-renewal, and differentiation. The Wnt pathway has been shown to be dysregulated in a variety of cancers. Porcupine is a membrane bound O-acyltransferase that palmitoylates Wnt. Inhibiting porcupine blocks the secretion of Wnt and effectively inhibits the Wnt pathway. Using high throughput screening, we have identified a number of novel porcupine inhibitors with diverse scaffolds. The pharmacophore requirements for our porcupine inhibitors were elucidated, and a pharmacophore model is proposed. Our compounds as well as all currently published porcupine inhibitors may be fitted to this model in low energy conformations with good superimposition of the pharmacophore elements. The model also explains the stereochemical requirements of our chiral porcupine inhibitors. The pharmacophore model was successfully used for designing 3 new series of porcupine inhibitors having a tricyclic xantine, a phtalimide, or a piperidine-maleimide scaffold.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Poulsen A,Ho SY,Wang W,Alam J,Jeyaraj DA,Ang SH,Tan ES,Lin GR,Cheong VW,Ke Z,Lee MA,Keller THdoi
10.1021/acs.jcim.5b00159subject
Has Abstractpub_date
2015-07-27 00:00:00pages
1435-48issue
7eissn
1549-9596issn
1549-960Xjournal_volume
55pub_type
杂志文章abstract：:Homology modeling is a reliable method of predicting the three-dimensional structures of proteins that lack NMR or X-ray crystallographic data. It employs the assumption that a structural resemblance exists between closely related proteins. Despite the availability of many crystal structures of possible templates, onl...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500001f
更新日期：2014-06-23 00:00:00
abstract：:There are only four derivatives of pseudouridine (Ψ) that are known to occur naturally in RNA as post-transcriptional modifications. We have studied the conformational consequences of pseudouridylation and further modifications using replica exchange molecular dynamics simulations at the nucleoside level, and the simu...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00369
更新日期：2020-10-26 00:00:00
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 relationshi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0500841
更新日期：2006-01-01 00:00:00
abstract：:We develop the idea that the use of ad hoc molecular descriptors in QSAR/QSPR studies is not an optimal solution. Instead, we propose to optimize these descriptors for the specific properties under study. In the case of topological indices (TIs) we propose the use of the generalized topological indices (GTIs), which a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600448b
更新日期：2007-05-01 00:00:00
abstract：:Mass spectrometric data are copious and generate a processing burden that is best dealt with programmatically. PythoMS is a collection of tools based on the Python programming language that assist researchers in creating figures and video output that is informative, clear, and visually compelling. The PythoMS framewor...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00055
更新日期：2019-04-22 00:00:00
abstract：:The reuptake of neurotransmitters by dopamine, norepinephrine, and serotonin transporters during neuronal transmission requires a sodium gradient. An "ionic mode" of binding proposes that aspartate anchors the ligand's positive charge but ignores the direct role of sodium in ligand binding seen in the only representat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700255d
更新日期：2008-07-01 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：:Finding a canonical ordering of the atoms in a molecule is a prerequisite for generating a unique representation of the molecule. The canonicalization of a molecule is usually accomplished by applying some sort of graph relaxation algorithm, the most common of which is the Morgan algorithm. There are known issues with...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00543
更新日期：2015-10-26 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
pub_type： 杂志文章
doi：10.1021/ci400724v
更新日期：2014-03-24 00:00:00
abstract：:Theoretical calculation of equilibrium dissociation constants is a very computationally demanding and time-consuming process since it requires an extremely accurate computation of the solvation free energy changes for each of the species involved. By correlating the minimum surface electrostatic potential (VS,min) on ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b01173
更新日期：2020-03-23 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：: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
pub_type： 杂志文章
doi：10.1021/ci800420z
更新日期：2009-06-01 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：:We introduce TICRA (transplant-insert-constrain-relax-assemble), a method for modeling the structure of unknown protein-ligand complexes using the X-ray crystal structures of homologous proteins and ligands with known activity. We present results from modeling the structures of protein kinase-inhibitor complexes using...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100256u
更新日期：2011-01-24 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：:Calcium and magnesium ions play important roles in many physicochemical processes. To facilitate the investigation of phenomena related to these ions that occur over large length and time scales, a coarse-grained force field (CGFF) is developed for MgCl2 and CaCl2 aqueous solutions. The ions are modeled by CG beads wi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00206
更新日期：2017-07-24 00:00:00
abstract：:Advances in computer-aided translation technology have made tremendous progress in accuracy in the past few years. Chemical Abstracts Service of the American Chemical Society summarizes scientific works from more than 50 languages and allows the users to search papers in nine selected languages. Currently, only the ab...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00274
更新日期：2020-07-27 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：:There is a growing public concern about the lack of reproducibility of experimental data published in peer-reviewed scientific literature. Herein, we review the most recent alerts regarding experimental data quality and discuss initiatives taken thus far to address this problem, especially in the area of chemical geno...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章,评审
doi：10.1021/acs.jcim.6b00129
更新日期：2016-07-25 00:00:00
abstract：:The study of chromatographic retention of natural products can be used to increase their identification speed in complex biological matrices. In this work, six variables were used to study the retention behavior in reversed phase liquid chromatography of 39 sesquiterpene lactones (SL) from an in-house database using c...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500581q
更新日期：2015-01-26 00:00:00
abstract：:Serotonin 5-HT6 receptor antagonists are thought to play an important role in the treatment of psychiatry, Alzheimer's disease, and probably obesity. To find novel and potent 5-HT6 antagonists and to provide a new idea for drug design, we used a ligand-based pharmacophore to perform the virtual screening of a commerci...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700160t
更新日期：2008-01-01 00:00:00
abstract：:The determination of the validity of a QSAR model when applied to new compounds is an important concern in the field of QSAR and QSPR modeling. Various scoring techniques can be applied to specific types of models. We present a technique with which we can state whether a new compound will be well predicted by a previo...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0497511
更新日期：2005-01-01 00:00:00
abstract：:Knowledge of the interactions between drugs and transporters is important for drug discovery and development as well as for the evaluation of their clinical safety. We recently developed a text-mining system for the automatic extraction of information on chemical-CYP3A4 interactions from the literature. This system is...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci4003188
更新日期：2013-10-28 00:00:00
abstract：:Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in the market against cancer until date. Computer-based or in silico virtual screening methods are often used in lead/hit discovery protocols. In this study, the "drug-likeness" of ~400 compounds from Africa...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5003697
更新日期：2014-09-22 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：: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 spatial sign is a multivariate extension of the concept of sign. Recently multivariate estimators of covariance structures based on spatial signs have been examined by various authors. These new estimators are found to be robust to outlying observations. From a computational point of view, estimators based on spat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050498u
更新日期：2006-05-01 00:00:00
abstract：:G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors, which is arguably the most important family of drug target. With the technology breakthroughs in X-ray crystallography and cryo-electron microscopy, more than 300 GPCR-ligand complex structures have been publicly reported since 2007,...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00699
更新日期：2020-09-28 00:00:00
abstract：:Universal generative topographic maps (GTMs) provide two-dimensional representations of chemical space selected for their "polypharmacological competence", that is, the ability to simultaneously represent meaningful activity and property landscapes, associated with many distinct targets and properties. Several such GT...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00650
更新日期：2019-01-28 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
