当前位置： SCI文献检索 > Journal of Chemical Information and Modeling期刊下所有文献 > Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures.

Discovery of wild-type and Y181C mutant non-nucleoside HIV-1 reverse transcriptase inhibitors using virtual screening with multiple protein structures.

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 commercially available compounds. Two of the structures are for WT-virus with different conformations of Tyr181, while the third structure incorporates the Y181C modification. Eventually nine compounds were purchased and assayed. Three of the compounds show low-micromolar antiviral activity toward either or both the wild-type and Y181C HIV-1 strains. The study illustrates a viable protocol to seek anti-HIV agents with enhanced resistance profiles.

journal_name

J Chem Inf Model

journal_title

Journal of chemical information and modeling

authors

Nichols SE,Domaoal RA,Thakur VV,Tirado-Rives J,Anderson KS,Jorgensen WL

doi

10.1021/ci900068k

subject

Has Abstract

pub_date

2009-05-01 00:00:00

pages

1272-9

issue

5

eissn

1549-9596

issn

1549-960X

journal_volume

49

pub_type

杂志文章

相关文献

Journal of Chemical Information and Modeling文献大全
  • Cheminformatics Modeling of Adverse Drug Responses by Clinically Relevant Mutants of Human Androgen Receptor.

    abstract：:The human androgen receptor (AR) is a ligand-activated transcription factor that plays a pivotal role in the development and progression of prostate cancer (PCa). Many forms of castration-resistant prostate cancer (CRPC) still rely on the AR for survival. Currently used antiandrogens face clinical limitations as drug ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.6b00400

    authors： Paul N,Carabet LA,Lallous N,Yamazaki T,Gleave ME,Rennie PS,Cherkasov A

    更新日期：2016-12-27 00:00:00

  • Molecular Structure-Based Large-Scale Prediction of Chemical-Induced Gene Expression Changes.

    abstract：:The quantitative structure-activity relationship (QSAR) approach has been used to model a wide range of chemical-induced biological responses. However, it had not been utilized to model chemical-induced genomewide gene expression changes until very recently, owing to the complexity of training and evaluating a very la...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.7b00281

    authors： Liu R,AbdulHameed MDM,Wallqvist A

    更新日期：2017-09-25 00:00:00

  • Chemical Topic Modeling: Exploring Molecular Data Sets Using a Common Text-Mining Approach.

    abstract：:Big data is one of the key transformative factors which increasingly influences all aspects of modern life. Although this transformation brings vast opportunities it also generates novel challenges, not the least of which is organizing and searching this data deluge. The field of medicinal chemistry is not different: ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.7b00249

    authors： Schneider N,Fechner N,Landrum GA,Stiefl N

    更新日期：2017-08-28 00:00:00

  • LiCABEDS II. Modeling of ligand selectivity for G-protein-coupled cannabinoid receptors.

    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

    authors： Ma C,Wang L,Yang P,Myint KZ,Xie XQ

    更新日期：2013-01-28 00:00:00

  • Imputation of Assay Bioactivity Data Using Deep Learning.

    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 correlation...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00768

    authors： Whitehead TM,Irwin BWJ,Hunt P,Segall MD,Conduit GJ

    更新日期：2019-03-25 00:00:00

  • Trans and Cis Conformations of the Antihypertensive Drug Valsartan Respectively Lock the Inactive and Active-like States of Angiotensin II Type 1 Receptor: A Molecular Dynamics Study.

    abstract：:Angiotensin II type 1 receptor (AT1R) is the principal regulator of blood pressure in humans. The overactivation of AT1R by the stimulation of angiotensin II would result in high blood pressure. To prevent hypertension, nonpeptide "sartan" drugs, such as valsartan (VST), have been developed to competitively block the ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00364

    authors： Wang L,Yan F

    更新日期：2018-10-22 00:00:00

  • Prediction and Experimental Confirmation of Novel Peripheral Cannabinoid-1 Receptor Antagonists.

    abstract：:Small molecules targeting peripheral CB1 receptors have therapeutic potential in a variety of disorders including obesity-related, hormonal, and metabolic abnormalities, while avoiding the psychoactive effects in the central nervous system. We applied our in-house algorithm, iterative stochastic elimination, to produc...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.9b00577

    authors： El-Atawneh S,Hirsch S,Hadar R,Tam J,Goldblum A

    更新日期：2019-09-23 00:00:00

  • Machine Learning Enhanced Spectrum Recognition Based on Computer Vision (SRCV) for Intelligent NMR Data Extraction.

    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

    authors： Jia W,Yang Z,Yang M,Cheng L,Lei Z,Wang X

    更新日期：2021-01-25 00:00:00

  • Use of 3D QSAR models for database screening: a feasibility study.

    abstract：:The applicability and scope of 3D QSAR methods (CoMFA, CoMSIA) to screen databases are examined. A protocol requiring minimal user intervention has been established to align training and test set molecules using FlexS. As model system isozymes of human carbonic anhydrase (hCA) are used, all results are exemplified stu...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci7002945

    authors： Hillebrecht A,Klebe G

    更新日期：2008-02-01 00:00:00

  • Computational evidence for the role of Arabidopsis thaliana UVR8 as UV-B photoreceptor and identification of its chromophore amino acids.

    abstract：:A homology model of the Arabidopsis thaliana UV resistance locus 8 (UVR8) protein is presented herein, showing a seven-bladed β-propeller conformation similar to the globular structure of RCC1. The UVR8 amino acid sequence contains a very high amount of conserved tryptophans, and the homology model shows that seven of...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci200017f

    authors： Wu M,Grahn E,Eriksson LA,Strid A

    更新日期：2011-06-27 00:00:00

  • Conformational analysis of macrocycles: finding what common search methods miss.

    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

    authors： Bonnet P,Agrafiotis DK,Zhu F,Martin E

    更新日期：2009-10-01 00:00:00

  • How Well Does the Extended Linear Interaction Energy Method Perform in Accurate Binding Free Energy Calculations?

    abstract：:With continually increased computer power, molecular mechanics force field-based approaches, such as the endpoint methods of molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and molecular mechanics generalized Born surface area (MM-GBSA), have been routinely applied in both drug lead identification and opt...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.0c00934

    authors： Hao D,He X,Ji B,Zhang S,Wang J

    更新日期：2020-12-28 00:00:00

  • A Grid Map Based Approach to Identify Nonobvious Ligand Design Opportunities in 3D Protein Structure Ensembles.

    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

    authors： Schmalhorst PS,Bergner A

    更新日期：2020-04-27 00:00:00

  • Pushing the Limits of Computational Structure-Based Drug Design with a Cryo-EM Structure: The Ca2+ Channel α2δ-1 Subunit as a Test Case.

    abstract：:Cryo-electron microscopy (cryo-EM) is emerging as a real alternative for structural elucidation. In spite of this, very few cryo-EM structures have been described so far as successful platforms for in silico drug design. Gabapentin and pregabalin are some of the most successful drugs in the treatment of epilepsy and n...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00347

    authors： Kotev M,Pascual R,Almansa C,Guallar V,Soliva R

    更新日期：2018-08-27 00:00:00

  • Truncated variants of the GCN4 transcription activator protein bind DNA with dramatically different dynamical motifs.

    abstract：:The yeast protein GCN4 is a transcriptional activator in the basic leucine zipper (bZip) family, whose distinguishing feature is the "chopstick-like" homodimer of alpha helices formed at the DNA-binding interface. While experiments have shown that truncated versions of the protein retain biologically relevant DNA-bind...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci500448e

    authors： McHarris DM,Barr DA

    更新日期：2014-10-27 00:00:00

  • Automated pharmacophore query optimization with genetic algorithms - a case study using the MC4R system.

    abstract：:Due to the recent availability of high quality small molecule databases, such as ZINC and PubChem,1,2 virtual screening is playing an even more important role in identifying biologically relevant molecules in drug discovery campaigns. The success of pharmacophore-based virtual screening (PBVS) relies largely on the ac...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci700089w

    authors： Jia L,Zou J,So SS,Sun H

    更新日期：2007-07-01 00:00:00

  • Study of chromatographic retention of natural terpenoids by chemoinformatic tools.

    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

    authors： Oliveira TB,Gobbo-Neto L,Schmidt TJ,Da Costa FB

    更新日期：2015-01-26 00:00:00

  • Novel inhibitors of trihydroxynaphthalene reductase with antifungal activity identified by ligand-based and structure-based virtual screening.

    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

    authors： Brunskole Svegelj M,Turk S,Brus B,Lanisnik Rizner T,Stojan J,Gobec S

    更新日期：2011-07-25 00:00:00

  • Regulation of JAK2 activation by Janus homology 2: evidence from molecular dynamics simulations.

    abstract：:Janus kinase 2 (JAK2) is a protein tyrosine kinase implicated in signaling by specific members of the cytokine receptor family. Although it has been established that the JAK2 tyrosine kinase is negatively regulated by the JAK homology 2 (JH2) pseudokinase domain, the underlying mechanism of JH2 mediated regulation rem...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci300308g

    authors： Wan S,Coveney PV

    更新日期：2012-11-26 00:00:00

  • Viscosity Prediction of Lubricants by a General Feed-Forward Neural Network.

    abstract：:Modern industrial lubricants are often blended with an assortment of chemical additives to improve the performance of the base stock. Machine learning-based predictive models allow fast and veracious derivation of material properties and facilitate novel and innovative material designs. In this study, we outline the d...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.9b01068

    authors： Loh GC,Lee HC,Tee XY,Chow PS,Zheng JW

    更新日期：2020-03-23 00:00:00

  • Protein kinases: docking and homology modeling reliability.

    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

    authors： Tuccinardi T,Botta M,Giordano A,Martinelli A

    更新日期：2010-08-23 00:00:00

  • Virtual drug screen schema based on multiview similarity integration and ranking aggregation.

    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

    authors： Kang H,Sheng Z,Zhu R,Huang Q,Liu Q,Cao Z

    更新日期：2012-03-26 00:00:00

  • Delineation of agonist binding to the human histamine H4 receptor using mutational analysis, homology modeling, and ab initio calculations.

    abstract：:A three-dimensional homology model of the human histamine H 4 receptor was developed to investigate the binding mode of a series of structurally diverse H 4-agonists, i.e. histamine, clozapine, and the recently described selective, nonimidazole agonist VUF 8430. Mutagenesis studies and docking of these ligands in a rh...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci700474a

    authors： Jongejan A,Lim HD,Smits RA,de Esch IJ,Haaksma E,Leurs R

    更新日期：2008-07-01 00:00:00

  • Relationships between Molecular Complexity, Biological Activity, and Structural Diversity.

    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

    authors： Schuffenhauer A,Brown N,Selzer P,Ertl P,Jacoby E

    更新日期：2006-03-01 00:00:00

  • Study of Data Set Modelability: Modelability, Rivality, and Weighted Modelability Indexes.

    abstract：:The knowledge of the capacity of a data set to be modeled in the first stages of the building of quantitative structure-activity relationship (QSAR) prediction models is an important issue because it might reduce the effort and time necessary to select or reject data sets and in refining the data set's composition. Th...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00188

    authors： Luque Ruiz I,Gómez-Nieto MÁ

    更新日期：2018-09-24 00:00:00

  • GPCR-Bench: A Benchmarking Set and Practitioners' Guide for G Protein-Coupled Receptor Docking.

    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

    authors： Weiss DR,Bortolato A,Tehan B,Mason JS

    更新日期：2016-04-25 00:00:00

  • Bridging molecular docking to membrane molecular dynamics to investigate GPCR-ligand recognition: the human A₂A adenosine receptor as a key study.

    abstract：:G protein-coupled receptors (GPCRs) represent the largest family of cell-surface receptors and about one-third of the actual targets of clinically used drugs. Following the progress made in the field of GPCRs structural determination, docking-based screening for novel potent and selective ligands is becoming an increa...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci400532b

    authors： Sabbadin D,Ciancetta A,Moro S

    更新日期：2014-01-27 00:00:00

  • Kinetic Models of Cyclosporin A in Polar and Apolar Environments Reveal Multiple Congruent Conformational States.

    abstract：:The membrane permeability of cyclic peptides and peptidomimetics, which are generally larger and more complex than typical drug molecules, is likely strongly influenced by the conformational behavior of these compounds in polar and apolar environments. The size and complexity of peptides often limit their bioavailabil...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.6b00251

    authors： Witek J,Keller BG,Blatter M,Meissner A,Wagner T,Riniker S

    更新日期：2016-08-22 00:00:00

  • Prediction of synthetic accessibility based on commercially available compound databases.

    abstract：:A compound's synthetic accessibility (SA) is an important aspect of drug design, since in some cases computer-designed compounds cannot be synthesized. There have been several reports on SA prediction, most of which have focused on the difficulties of synthetic reactions based on retro-synthesis analyses, reaction dat...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci500568d

    authors： Fukunishi Y,Kurosawa T,Mikami Y,Nakamura H

    更新日期：2014-12-22 00:00:00

  • Structure-based CoMFA as a predictive model - CYP2C9 inhibitors as a test case.

    abstract：:In this study, we tried to establish a general scheme to create a model that could predict the affinity of small compounds to their target proteins. This scheme consists of a search for ligand-binding sites on a protein, a generation of bound conformations (poses) of ligands in each of the sites by docking, identifica...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci800313h

    authors： Yasuo K,Yamaotsu N,Gouda H,Tsujishita H,Hirono S

    更新日期：2009-04-01 00:00:00