当前位置： SCI文献检索 > Journal of Chemical Information and Modeling期刊下所有文献 > Prediction of cytochrome P450 xenobiotic metabolism: tethered docking and reactivity derived from ligand molecular orbital analysis.

Prediction of cytochrome P450 xenobiotic metabolism: tethered docking and reactivity derived from ligand molecular orbital analysis.

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 paper describes a reactivity approach for predicting SoM whereby reactivity is derived directly from the ground state ligand molecular orbital analysis, calculated using Density Functional Theory, using a novel implementation of the average local ionization energy. Thus each potential SoM is sampled in the context of the whole ligand, in contrast to other popular approaches where activation energies are calculated for a predefined database of molecular fragments and assigned to matching moieties in a query ligand. In addition, one of the first descriptions of molecular dynamics of cytochrome P450 (CYP) isoforms 3A4, 2D6, and 2C9 in their Compound I state is reported, and, from the representative protein structures obtained, an analysis and evaluation of various docking approaches using GOLD is performed. In particular, a covalent docking approach is described coupled with the modeling of important electrostatic interactions between CYP and ligand using spherical constraints. Combining the docking and reactivity results, obtained using standard functionality from common docking and quantum chemical applications, enables a SoM to be identified in the top 2 predictions for 75%, 80%, and 78% of the data sets for 3A4, 2D6, and 2C9, respectively, results that are accessible and competitive with other recently published prediction tools.

journal_name

J Chem Inf Model

journal_title

Journal of chemical information and modeling

authors

Tyzack JD,Williamson MJ,Torella R,Glen RC

doi

10.1021/ci400058s

subject

Has Abstract

pub_date

2013-06-24 00:00:00

pages

1294-305

issue

6

eissn

1549-9596

issn

1549-960X

journal_volume

53

pub_type

杂志文章

相关文献

Journal of Chemical Information and Modeling文献大全
  • Discovery of Inhibitors of Four Bromodomains by Fragment-Anchored Ligand Docking.

    abstract：:The high-throughput docking protocol called ALTA-VS (anchor-based library tailoring approach for virtual screening) was developed in 2005 for the efficient in silico screening of large libraries of compounds by preselection of only those molecules that have optimal fragments (anchors) for the protein target. Here we p...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.7b00336

    authors： Marchand JR,Dalle Vedove A,Lolli G,Caflisch A

    更新日期：2017-10-23 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

  • Periodic cages.

    abstract：:Various cages are constructed by using three types of caps: f-cap (derived from spherical fullerenes by deleting zones of various size), kf-cap (obtainable by cutting off the polar ring, of size k), and t-cap ("tubercule"-cap). Building ways are presented, some of them being possible isomerization routes in the real c...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci049738g

    authors： Diudea MV,Nagy CL,Silaghi-Dumitrescu I,Graovac A,Janezic D,Vikić-Topić D

    更新日期：2005-03-01 00:00:00

  • Conformator: A Novel Method for the Generation of Conformer Ensembles.

    abstract：:Computer-aided drug design methods such as docking, pharmacophore searching, 3D database searching, and the creation of 3D-QSAR models need conformational ensembles to handle the flexibility of small molecules. Here, we present Conformator, an accurate and effective knowledge-based algorithm for generating conformer e...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00704

    authors： Friedrich NO,Flachsenberg F,Meyder A,Sommer K,Kirchmair J,Rarey M

    更新日期：2019-02-25 00:00:00

  • Concept-based semi-automatic classification of drugs.

    abstract：:The anatomical therapeutic chemical (ATC) classification system maintained by the World Health Organization provides a global standard for the classification of medical substances and serves as a source for drug repurposing research. Nevertheless, it lacks several drugs that are major players in the global drug market...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci9000844

    authors： Gurulingappa H,Kolárik C,Hofmann-Apitius M,Fluck J

    更新日期：2009-08-01 00:00:00

  • Combinatorial × computational × cheminformatics (C3) approach to characterization of congeneric libraries of organic pollutants.

    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

    authors： Haranczyk M,Urbaszek P,Ng EG,Puzyn T

    更新日期：2012-11-26 00:00:00

  • Benchmark data sets for structure-based computational target prediction.

    abstract：:Structure-based computational target prediction methods identify potential targets for a bioactive compound. Methods based on protein-ligand docking so far face many challenges, where the greatest probably is the ranking of true targets in a large data set of protein structures. Currently, no standard data sets for ev...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci500131x

    authors： Schomburg KT,Rarey M

    更新日期：2014-08-25 00:00:00

  • Comparison of Implicit and Explicit Solvation Models for Iota-Cyclodextrin Conformation Analysis from Replica Exchange Molecular Dynamics.

    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

    authors： Khuntawee W,Kunaseth M,Rungnim C,Intagorn S,Wolschann P,Kungwan N,Rungrotmongkol T,Hannongbua S

    更新日期：2017-04-24 00:00:00

  • Development of an informatics platform for therapeutic protein and peptide analytics.

    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...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci400333x

    authors： Hansen MR,Villar HO,Feyfant E

    更新日期：2013-10-28 00:00:00

  • Instrument monitoring, data sharing, and archiving using Common Instrument Middleware Architecture (CIMA).

    abstract：:The Common Instrument Middleware Architecture (CIMA) aims at Grid-enabling a wide range of scientific instruments and sensors to enable easy access to and sharing and storage of data produced by these instruments and sensors. This paper describes the implementation of CIMA applied to the field of single-crystal X-ray ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci050368l

    authors： Bramley R,Chiu K,Devadithya T,Gupta N,Hart C,Huffman JC,Huffman K,Ma Y,McMullen DF

    更新日期：2006-05-01 00:00:00

  • Evaluating QM/MM Free Energy Surfaces for Ranking Cysteine Protease Covalent Inhibitors.

    abstract：:One tactic for cysteine protease inhibition is to form a covalent bond between an electrophilic atom of the inhibitor and the thiol of the catalytic cysteine. In this study, we evaluate the reaction free energy obtained from a hybrid quantum mechanical/molecular mechanical (QM/MM) free energy profile as a predictor of...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.9b00847

    authors： da Costa CHS,Bonatto V,Dos Santos AM,Lameira J,Leitão A,Montanari CA

    更新日期：2020-02-24 00:00:00

  • Binding Residence Time through Scaled Molecular Dynamics: A Prospective Application to hDAAO Inhibitors.

    abstract：:Traditionally, a drug potency is expressed in terms of thermodynamic quantities, mostly Kd, and empirical IC50 values. Although binding affinity as an estimate of drug activity remains relevant, it is increasingly clear that it is also important to include (un)binding kinetic parameters in the characterization of pote...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00518

    authors： Bernetti M,Rosini E,Mollica L,Masetti M,Pollegioni L,Recanatini M,Cavalli A

    更新日期：2018-11-26 00:00:00

  • Develop and test a solvent accessible surface area-based model in conformational entropy calculations.

    abstract：:It is of great interest in modern drug design to accurately calculate the free energies of protein-ligand or nucleic acid-ligand binding. MM-PBSA (molecular mechanics Poisson-Boltzmann surface area) and MM-GBSA (molecular mechanics generalized Born surface area) have gained popularity in this field. For both methods, ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci300064d

    authors： Wang J,Hou T

    更新日期：2012-05-25 00:00:00

  • Descriptor Data Bank (DDB): A Cloud Platform for Multiperspective Modeling of Protein-Ligand Interactions.

    abstract：:Protein-ligand (PL) interactions play a key role in many life processes such as molecular recognition, molecular binding, signal transmission, and cell metabolism. Examples of interaction forces include hydrogen bonding, hydrophobic effects, steric clashes, electrostatic contacts, and van der Waals attractions. Curren...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.7b00310

    authors： Ashtawy HM,Mahapatra NR

    更新日期：2018-01-22 00:00:00

  • Substituted 4,5'-Bithiazoles as Catalytic Inhibitors of Human DNA Topoisomerase IIα.

    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

    authors： Bergant Loboda K,Janežič M,Štampar M,Žegura B,Filipič M,Perdih A

    更新日期：2020-07-27 00:00:00

  • GESSE: Predicting Drug Side Effects from Drug-Target Relationships.

    abstract：:The in silico prediction of unwanted side effects (SEs) caused by the promiscuous behavior of drugs and their targets is highly relevant to the pharmaceutical industry. Considerable effort is now being put into computational and experimental screening of several suspected off-target proteins in the hope that SEs might...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.5b00120

    authors： Pérez-Nueno VI,Souchet M,Karaboga AS,Ritchie DW

    更新日期：2015-09-28 00:00:00

  • Novel Consensus Architecture To Improve Performance of Large-Scale Multitask Deep Learning QSAR Models.

    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

    authors： Zakharov AV,Zhao T,Nguyen DT,Peryea T,Sheils T,Yasgar A,Huang R,Southall N,Simeonov A

    更新日期：2019-11-25 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

  • 3D-QSAR and docking studies of selective GSK-3beta inhibitors. Comparison with a thieno[2,3-b]pyrrolizinone derivative, a new potential lead for GSK-3beta ligands.

    abstract：:The three-dimensional structures of 3-anilino-4-arylmaleimides, selective GSK-3beta inhibitors, were correlated to their biological affinities by 3D-QSAR studies (CoMFA method). The cocrystallographic data of GSK-3beta vs 3-anilino-4-arylmaleimide allowed us to compare 3D-QSAR results to experimental intermolecular in...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci050008y

    authors： Lescot E,Bureau R,Sopkova-de Oliveira Santos J,Rochais C,Lisowski V,Lancelot JC,Rault S

    更新日期：2005-05-01 00:00:00

  • Dihedral-based segment identification and classification of biopolymers I: proteins.

    abstract：:A new structure classification scheme for biopolymers is introduced, which is solely based on main-chain dihedral angles. It is shown that by dividing a biopolymer into segments containing two central residues, a local classification can be performed. The method is referred to as DISICL, short for Dihedral-based Segme...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci400541d

    authors： Nagy G,Oostenbrink C

    更新日期：2014-01-27 00:00:00

  • Equally Weighted Multiscale Elastic Network Model and Its Comparison with Traditional and Parameter-Free Models.

    abstract：:Dynamical properties of proteins play an essential role in their function exertion. The elastic network model (ENM) is an effective and efficient tool in characterizing the intrinsic dynamical properties encoded in biomacromolecule structures. The Gaussian network model (GNM) and anisotropic network model (ANM) are th...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.0c01178

    authors： Gong W,Liu Y,Zhao Y,Wang S,Han Z,Li C

    更新日期：2021-01-26 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

  • Nonadditivity Analysis.

    abstract：:We introduce the statistics behind a novel type of SAR analysis named "nonadditivity analysis". On the basis of all pairs of matched pairs within a given data set, the approach analyzes whether the same transformations between related molecules have the same effect, i.e., whether they are additive. Assuming that the e...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.9b00631

    authors： Kramer C

    更新日期：2019-09-23 00:00:00

  • Protein flexibility in virtual screening: the BACE-1 case study.

    abstract：:Simulating protein flexibility is a major issue in the docking-based drug-design process for which a single methodological solution does not exist. In our search of new anti-Alzheimer ligands, we were faced with the challenge of including receptor plasticity in a virtual screening campaign aimed at finding new β-secre...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci300390h

    authors： Cosconati S,Marinelli L,Di Leva FS,La Pietra V,De Simone A,Mancini F,Andrisano V,Novellino E,Goodsell DS,Olson AJ

    更新日期：2012-10-22 00:00:00

  • Learning To Predict Reaction Conditions: Relationships between Solvent, Molecular Structure, and Catalyst.

    abstract：:Reaction databases provide a great deal of useful information to assist planning of experiments but do not provide any interpretation or chemical concepts to accompany this information. In this work, reactions are labeled with experimental conditions, and network analysis shows that consistencies within clusters of da...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.9b00313

    authors： Walker E,Kammeraad J,Goetz J,Robo MT,Tewari A,Zimmerman PM

    更新日期：2019-09-23 00:00:00

  • Allosteric Response of DNA Recognition Helices of Catabolite Activator Protein to cAMP and DNA Binding.

    abstract：:The homodimeric catabolite activator protein (CAP) regulates the transcription of several bacterial genes based on the cellular concentration of cyclic adenosine monophosphate (cAMP). The binding of cAMP to CAP triggers allosteric communication between the cAMP binding domains (CBD) and DNA binding domains (DBD) of CA...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.0c00617

    authors： Prabhakant A,Panigrahi A,Krishnan M

    更新日期：2020-12-28 00:00:00

  • Cyclohexane-Based Scaffold Molecules Acting as Anion Transport, Anionophores, via Noncovalent Interactions.

    abstract：:A theoretical study of a variety of cyclohexane-based anion transporters interacting with the chloride anion has been conducted using density functional theory. The calculations have been performed in the gas phase but also, in order to describe the solvation effects on the interaction, two different solvents-chlorofo...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.9b00154

    authors： Sánchez-Sanz G,Trujillo C

    更新日期：2019-05-28 00:00:00

  • Effect of input differences on the results of docking calculations.

    abstract：:The sensitivity of docking calculations to the geometry of the input ligand was studied. It was found that even small changes in the ligand input conformation can lead to large differences in the geometries and scores of the resulting docked poses. The accuracy of docked poses produced from different ligand input stru...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci9000629

    authors： Feher M,Williams CI

    更新日期：2009-07-01 00:00:00

  • Influence of Descriptor Implementation on Compound Ranking Based on Multiparameter Assessment.

    abstract：:Most of the common molecular descriptors have numerous different implementations. This can influence the results of compound prioritization based on the multiparameter assessment (MPA) approach that allows a medicinal chemist to simultaneously analyze and achieve the desired balance of the diverse and often conflictin...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.7b00734

    authors： Sosnina EA,Osolodkin DI,Radchenko EV,Sosnin S,Palyulin VA

    更新日期：2018-05-29 00:00:00

  • Discovery of New SIRT2 Inhibitors by Utilizing a Consensus Docking/Scoring Strategy and Structure-Activity Relationship Analysis.

    abstract：:SIRT2, which is a NAD+ (nicotinamide adenine dinucleotide) dependent deacetylase, has been demonstrated to play an important role in the occurrence and development of a variety of diseases such as cancer, ischemia-reperfusion, and neurodegenerative diseases. Small molecule inhibitors of SIRT2 are thought to be potenti...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.6b00714

    authors： Huang S,Song C,Wang X,Zhang G,Wang Y,Jiang X,Sun Q,Huang L,Xiang R,Hu Y,Li L,Yang S

    更新日期：2017-04-24 00:00:00