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-methylurapidil, into two alpha1A receptor models, active and inactive. The best docking complexes for both agonists had hydrophilic interactions with D106, while neither antagonist did. Prazosin and oxymetazoline had hydrophobic interactions with F308 and F312. We predict from our study that the active state is stabilized by the interaction of F193 with I114, L197, V278, F281, and V282. The active state is further stabilized by the interaction of F312 with L75, V79, and L80. We also predict that the inactive state of the receptor is stabilized by the interaction of F312 with W102, F288, and M292.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Asher WB,Hoskins SN,Slasor LA,Morris DH,Cook EM,Bautista DLdoi
10.1021/ci700026vsubject
Has Abstractpub_date
2007-09-01 00:00:00pages
1906-12issue
5eissn
1549-9596issn
1549-960Xjournal_volume
47pub_type
杂志文章abstract：:Molecular docking programs are widely used modeling tools for predicting ligand binding modes and structure based virtual screening. In this study, six molecular docking programs (DOCK, FlexX, GLIDE, ICM, PhDOCK, and Surflex) were evaluated using metrics intended to assess docking pose and virtual screening accuracy. ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900056c
更新日期：2009-06-01 00:00:00
abstract：:The ligand binding determinants for the angiotensin II type 1 receptor (AT1R), a G protein-coupled receptor (GPCR), have been characterized by means of computer simulations. As a first step, a pharmacophore model of various known AT1R ligands exhibiting a wide range of binding affinities was generated. Second, a struc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2013-11-25 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 momentum gained by research on biologics has not been met yet with equal thrust on the informatics side. There is a noticeable lack of software for data management that empowers the bench scientists working on the development of biologic therapeutics. SARvision|Biologics is a tool to analyze data associated with b...
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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...
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pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00408
更新日期：2019-07-22 00:00:00
abstract：:Large ring cyclodextrins have become increasingly important for drug delivery applications. In this work, we have performed replica-exchange molecular dynamics simulations using both implicit and explicit water solvation models to study the conformational diversity of iota-cyclodextrin containing 14 α-1,4 glycosidic l...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00595
更新日期：2017-04-24 00:00:00
abstract：:In this study, we used the Martini Coarse-Grained model with no applied restraints to predict the binding mode of some peptides to G-Protein Coupled Receptors (GPCRs). Both the Neurotensin-1 and the chemokine CXCR4 receptors were used as test cases. Their ligands, NTS8-13 and CVX15 peptides, respectively, were initial...
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pub_type： 杂志文章
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更新日期：2017-03-27 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
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更新日期：2016-07-25 00:00:00
abstract：:The ongoing search for fast Li-ion conducting solid electrolytes has driven the deployment surge on density functional theory (DFT) computation and materials informatics for exploring novel chemistries before actual experimental testing. Existing structure prototypes can now be readily evaluated beforehand not only to...
journal_title：Journal of chemical information and modeling
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更新日期：2015-06-22 00:00:00
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...
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更新日期：2012-01-23 00:00:00
abstract：:A new web portal for the CHARMM macromolecular modeling package, CHARMMing (CHARMM interface and graphics, http://www.charmming.org), is presented. This tool provides a user-friendly interface for the preparation, submission, monitoring, and visualization of molecular simulations (i.e., energy minimization, solvation,...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800133b
更新日期：2008-09-01 00:00:00
abstract：:Scoring the activity of compounds in phenotypic high-throughput assays presents a unique challenge because of the limited resolution and inherent measurement error of these assays. Techniques that leverage the structural similarity of compounds within an assay can be used to improve the hit-recovery rate from screenin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050087d
更新日期：2005-11-01 00:00:00
abstract：:The emergence of a large amount of pharmacological, genomic, and network knowledge data provides new challenges and opportunities for drug discovery and development. Identification of real small-molecule drug (SM)-miRNA associations is not only important in the development of effective drug repositioning but also cruc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00244
更新日期：2020-08-24 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：: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：:The efficiency of automated compound screening is heavily influenced by the design and the quality of the screening libraries used. We recently reported on the assembly of one diverse and one target-focused lead-like screening library. Using data from 15 enzyme-based screenings conducted using these libraries, their p...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300382f
更新日期：2013-03-25 00:00:00
abstract：:Functional diversity of the three-finger-protein domain (TFPD) had been acquired via hypervariability of some sequence positions and extensive insertion/deletion of short AA-segments that caused multidimensional drift of several sequence attributes such as the overall (HI) and local hydrophobicity levels, the isoelect...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00322
更新日期：2015-09-28 00:00:00
abstract：:MHC class II molecules bind peptides derived from extracellular proteins that have been ingested by antigen-presenting cells and display them to the immune system. Peptide loading occurs within the antigen-presenting cell and is facilitated by HLA-DM. HLA-DM stabilizes the open conformation of the MHCII binding groove...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00104
更新日期：2019-06-24 00:00:00
abstract：:Reaction classification has important applications, and many approaches to classification have been applied. Our own algorithm tests all maximum common substructures (MCS) between all reactant and product molecules in order to find an atom mapping containing the minimum chemical distance (MCD). Recent publications hav...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400442f
更新日期：2013-11-25 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：:Since many projects at pharmaceutical organizations get their start from a high-throughput screening (HTS) campaign, improving the quality of the HTS deck can improve the likelihood of discovering a high-quality lead molecule that can be progressed to a drug candidate. Over the past decade, Janssen has implemented sev...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
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更新日期：2018-10-22 00:00:00
abstract：:Increasing protein kinase C (PKC) activity is of potential therapeutic value. Its activation involves an interaction between the C1 domain and diacylglycerol (DAG) at intracellular membrane surfaces; DAG mimetics hold promise as new drugs. We previously developed the isophthalate derivative HMI-1a3, an effective but h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00624
更新日期：2020-11-23 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...
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更新日期：2013-06-24 00:00:00
abstract：:The goal of the present study was to ascertain the differential performance of a long molecular dynamics trajectory versus several shorter ones starting from different points in the phase space and covering the same sampling time. For this purpose, we selected the 16-mer peptide Bak16BH3 as a model for study and carri...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00347
更新日期：2016-10-24 00:00:00
abstract：:Atomic neural networks (ANNs) constitute a class of machine learning methods for predicting potential energy surfaces and physicochemical properties of molecules and materials. Despite many successes, developing interpretable ANN architectures and implementing existing ones efficiently are still challenging. This call...
journal_title：Journal of chemical information and modeling
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更新日期：2020-03-23 00:00:00
abstract：:Random Forest regression (RF), Partial-Least-Squares (PLS) regression, Support Vector Machines (SVM), and Artificial Neural Networks (ANN) were used to develop QSPR models for the prediction of aqueous solubility, based on experimental data for 988 organic molecules. The Random Forest regression model predicted aqueou...
journal_title：Journal of chemical information and modeling
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更新日期：2007-01-01 00:00:00
abstract：:An essential feature of all practical de novo molecule generating programs is the ability to focus the potential combinatorial explosion of grown molecules on a desired chemical space. It is a daunting task to balance the generation of new molecules with limitations on growth that produce desired features such as stab...
journal_title：Journal of chemical information and modeling
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更新日期：2009-07-01 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...
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更新日期：2015-01-26 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
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更新日期：2016-01-25 00:00:00
abstract：:The concept of chemoisosterism of protein environments is introduced as the complementary property to bioisosterism of chemical fragments. In the same way that two chemical fragments are considered bioisosteric if they can bind to the same protein environment, two protein environments will be considered chemoisosteric...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci3002974
更新日期：2013-02-25 00:00:00
