Cross-docking of inhibitors into CDK2 structures. 2.

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 was observed with both methods; furthermore, Glide showed modest log(IC50)/score correlations. In this part of the study, the effect of combining docking results from multiple protein conformations in a consensus fashion was probed. This approach enhanced docking accuracy only for Glide, which was attributed to the nature of its scoring function. For log(IC50)/score correlations, particular emphasis was placed on considering only scores from correctly docked poses. Using multiple instead of single protein structures showed an improvement in the correlations. Validation sets and scrambling experiments were used to examine the statistical significance and predictivity of these correlations. Rather than actual improvements in scoring accuracy, docking to multiple protein conformations produced overfitting artifacts.

journal_name

J Chem Inf Model

authors

Voigt JH,Elkin C,Madison VS,Duca JS

doi

10.1021/ci700428d

subject

Has Abstract

pub_date

2008-03-01 00:00:00

pages

669-78

issue

3

eissn

1549-9596

issn

1549-960X

journal_volume

48

pub_type

杂志文章
  • Synergistic use of compound properties and docking scores in neural network modeling of CYP2D6 binding: predicting affinity and conformational sampling.

    abstract::Cytochrome P450 2D6 (CYP2D6) is used to develop an approach for predicting affinity and relevant binding conformation(s) for highly flexible binding sites. The approach combines the use of docking scores and compound properties as attributes in building a neural network (NN) model. It begins by identifying segments of...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci600267k

    authors: Bazeley PS,Prithivi S,Struble CA,Povinelli RJ,Sem DS

    更新日期:2006-11-01 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

  • Algorithm for reaction classification.

    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

    authors: Kraut H,Eiblmaier J,Grethe G,Löw P,Matuszczyk H,Saller H

    更新日期:2013-11-25 00:00:00

  • SARANEA: a freely available program to mine structure-activity and structure-selectivity relationship information in compound data sets.

    abstract::We introduce SARANEA, an open-source Java application for interactive exploration of structure-activity relationship (SAR) and structure-selectivity relationship (SSR) information in compound sets of any source. SARANEA integrates various SAR and SSR analysis functions and utilizes a network-like similarity graph data...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci900416a

    authors: Lounkine E,Wawer M,Wassermann AM,Bajorath J

    更新日期:2010-01-01 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

  • Metabotropic glutamate receptor-mediated currents at the climbing fiber to Purkinje cell synapse.

    abstract::Different forms of synaptic plasticity in the cerebellum expressed at the synapses onto Purkinje cells (PCs) are mediated by membrane metabotropic glutamate receptors (mGluRs). There are three main mGluR groups with a total of 8 subtypes. Although mGluRs are also found at the climbing fiber (CF) to PC synapses, the di...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci050161s

    authors: Andjus PR,Bajić A,Zhu L,Strata P

    更新日期:2005-11-01 00:00:00

  • Comparative analysis of binding energy of chymostatin with human cathepsin A and its homologous proteins by molecular orbital calculation.

    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

    authors: Yoshida T,Lepp Z,Kadota Y,Satoh Y,Itoh K,Chuman H

    更新日期:2006-09-01 00:00:00

  • Long-range effects of a peripheral mutation on the enzymatic activity of cytochrome P450 1A2.

    abstract::The human cytochrome P450 1A2 is an important drug metabolizing and procarcinogen activating enzyme. An experimental study found that a peripheral mutation, F186L, at ∼26 Å away from the enzyme's active site, caused a significant reduction in the enzymatic activity of 1A2 deethylation reactions. In this paper, we expl...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci200112b

    authors: Zhang T,Liu LA,Lewis DF,Wei DQ

    更新日期:2011-06-27 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

  • 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

  • Exploration of Interfacial Hydration Networks of Target-Ligand Complexes.

    abstract::Interfacial hydration strongly influences interactions between biomolecules. For example, drug-target complexes are often stabilized by hydration networks formed between hydrophilic residues and water molecules at the interface. Exhaustive exploration of hydration networks is challenging for experimental as well as th...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.5b00638

    authors: Jeszenői N,Bálint M,Horváth I,van der Spoel D,Hetényi C

    更新日期:2016-01-25 00:00:00

  • Binding Interactions of Ergotamine and Dihydroergotamine to 5-Hydroxytryptamine Receptor 1B (5-HT1b) Using Molecular Dynamics Simulations and Dynamic Network Analysis.

    abstract::Ergotamine (ERG) and dihydroergotamine (DHE), common migraine drugs, have small structural differences but lead to clinically important distinctions in their pharmacological profiles. For example, DHE is less potent than ERG by about 10-fold at the 5-hydroxytrptamine receptor 1B (5-HT1B). Although the high-resolution ...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b01082

    authors: Sullivan HJ,Tursi A,Moore K,Campbell A,Floyd C,Wu C

    更新日期:2020-03-23 00:00:00

  • Get Your Atoms in Order--An Open-Source Implementation of a Novel and Robust Molecular Canonicalization Algorithm.

    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

    authors: Schneider N,Sayle RA,Landrum GA

    更新日期:2015-10-26 00:00:00

  • Computational Insight Into the Mechanism of SARS-CoV-2 Membrane Fusion.

    abstract::Membrane fusion, a key step in the early stages of virus propagation, allows the release of the viral genome in the host cell cytoplasm. The process is initiated by fusion peptides that are small, hydrophobic components of viral membrane-embedded glycoproteins and are typically conserved within virus families. Here, w...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.0c01231

    authors: Borkotoky S,Dey D,Banerjee M

    更新日期:2021-01-25 00:00:00

  • Improving Protein-Ligand Docking Results with High-Throughput Molecular Dynamics Simulations.

    abstract::Structure-based virtual screening relies on classical scoring functions that often fail to reliably discriminate binders from nonbinders. In this work, we present a high-throughput protein-ligand complex molecular dynamics (MD) simulation that uses the output from AutoDock Vina to improve docking results in distinguis...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.0c00057

    authors: Guterres H,Im W

    更新日期:2020-04-27 00:00:00

  • Mechanism of Hormone Peptide Activation of a GPCR: Angiotensin II Activated State of AT1R Initiated by van der Waals Attraction.

    abstract::We present a succession of structural changes involved in hormone peptide activation of a prototypical GPCR. Microsecond molecular dynamics simulation generated conformational ensembles reveal propagation of structural changes through key "microswitches" within human AT1R bound to native hormone. The endocrine octa-pe...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.8b00583

    authors: Singh KD,Unal H,Desnoyer R,Karnik SS

    更新日期:2019-01-28 00:00:00

  • Alanine Scanning Effects on the Biochemical and Biophysical Properties of Intrinsically Disordered Proteins: A Case Study of the Histidine to Alanine Mutations in Amyloid-β42.

    abstract::Alanine scanning is a tool in molecular biology that is commonly used to evaluate the contribution of a specific amino acid residue to the stability and function of a protein. Additionally, this tool is also used to understand whether the side chain of a specific amino acid residue plays a role in the protein's bioact...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.8b00926

    authors: Coskuner-Weber O,Uversky VN

    更新日期:2019-02-25 00:00:00

  • Heteroaromatic π-stacking energy landscapes.

    abstract::In this study we investigate π-stacking interactions of a variety of aromatic heterocycles with benzene using dispersion corrected density functional theory. We calculate extensive potential energy surfaces for parallel-displaced interaction geometries. We find that dispersion contributes significantly to the interact...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci500183u

    authors: Huber RG,Margreiter MA,Fuchs JE,von Grafenstein S,Tautermann CS,Liedl KR,Fox T

    更新日期:2014-05-27 00:00:00

  • Retrospect and Prospect of Single Particle Cryo-Electron Microscopy: The Class of Integral Membrane Proteins as an Example.

    abstract::A giant technological leap in the field of cryo-electron microscopy (cryo-EM) has assured the achievement of near-atomic resolution structures of biological macromolecules. As a recognition of this accomplishment, the Nobel Prize in Chemistry was awarded in 2017 to Jacques Dubochet, Joachim Frank, and Richard Henderso...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.9b01015

    authors: Akbar S,Mozumder S,Sengupta J

    更新日期:2020-05-26 00:00:00

  • Scaling predictive modeling in drug development with cloud computing.

    abstract::Growing data sets with increased time for analysis is hampering predictive modeling in drug discovery. Model building can be carried out on high-performance computer clusters, but these can be expensive to purchase and maintain. We have evaluated ligand-based modeling on cloud computing resources where computations ar...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci500580y

    authors: Moghadam BT,Alvarsson J,Holm M,Eklund M,Carlsson L,Spjuth O

    更新日期:2015-01-26 00:00:00

  • Phytochemical informatics of traditional Chinese medicine and therapeutic relevance.

    abstract::Distribution patterns of 8411 compounds from 240 Chinese herbs were analyzed in relation to the herbal categories of traditional Chinese medicine (TCM), using Random Forest (RF) and self-organizing maps (SOM). RF was used first to construct TCM profiles of individual compounds, which describe their affinities for 28 m...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci700155t

    authors: Ehrman TM,Barlow DJ,Hylands PJ

    更新日期:2007-11-01 00:00:00

  • Molecular Mechanism underlying PRMT1 Dimerization for SAM Binding and Methylase Activity.

    abstract::Protein arginine methyltransferases (PRMTs) catalyze the posttranslational methylation of arginine, which is important in a range of biological processes, including epigenetic regulation, signal transduction, and cancer progression. Although previous studies of PRMT1 mutants suggest that the dimerization arm and the N...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.5b00454

    authors: Zhou R,Xie Y,Hu H,Hu G,Patel VS,Zhang J,Yu K,Huang Y,Jiang H,Liang Z,Zheng YG,Luo C

    更新日期:2015-12-28 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

  • ThermoData Engine (TDE): software implementation of the dynamic data evaluation concept. 9. Extensible thermodynamic constraints for pure compounds and new model developments.

    abstract::ThermoData Engine (TDE) is the first full-scale software implementation of the dynamic data evaluation concept, as reported in this journal. The present article describes the background and implementation for new additions in latest release of TDE. Advances are in the areas of program architecture and quality improvem...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci4005699

    authors: Diky V,Chirico RD,Muzny CD,Kazakov AF,Kroenlein K,Magee JW,Abdulagatov I,Frenkel M

    更新日期:2013-12-23 00:00:00

  • Accurate Hit Estimation for Iterative Screening Using Venn-ABERS Predictors.

    abstract::Iterative screening has emerged as a promising approach to increase the efficiency of high-throughput screening (HTS) campaigns in drug discovery. By learning from a subset of the compound library, inferences on what compounds to screen next can be made by predictive models. One of the challenges of iterative screenin...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.8b00724

    authors: Buendia R,Kogej T,Engkvist O,Carlsson L,Linusson H,Johansson U,Toccaceli P,Ahlberg E

    更新日期:2019-03-25 00:00:00

  • Molecular Simulation of αvβ6 Integrin Inhibitors.

    abstract::The urgent need for new treatments for the chronic lung disease idiopathic pulmonary fibrosis (IPF) motivates research into antagonists of the RGD binding integrin αvβ6, a protein linked to the initiation and progression of the disease. Molecular dynamics (MD) simulations of αvβ6 in complex with its natural ligand, pr...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.0c00254

    authors: Guest EE,Oatley SA,Macdonald SJF,Hirst JD

    更新日期:2020-11-23 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

  • CRDOCK: an ultrafast multipurpose protein-ligand docking tool.

    abstract::An ultrafast docking and virtual screening program, CRDOCK, is presented that contains (1) a search engine that can use a variety of sampling methods and an initial energy evaluation function, (2) several energy minimization algorithms for fine tuning the binding poses, and (3) different scoring functions. This modula...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci300194a

    authors: Cortés Cabrera Á,Klett J,Dos Santos HG,Perona A,Gil-Redondo R,Francis SM,Priego EM,Gago F,Morreale A

    更新日期:2012-08-27 00:00:00

  • Mechanisms for Flavin-Mediated Oxidation: Hydride or Hydrogen-Atom Transfer?

    abstract::Flavins are versatile biological cofactors which catalyze proton-coupled electron transfers (PCET) with varying number and coupling of electrons. Flavin-mediated oxidations of nicotinamide adenine dinucleotide (NADH) and of succinate, initial redox reactions in cellular respiration, were examined here with multiconfig...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/acs.jcim.0c00945

    authors: Curtolo F,Arantes GM

    更新日期:2020-12-28 00:00:00

  • Development of novel statistical potentials describing cation-pi interactions in proteins and comparison with semiempirical and quantum chemistry approaches.

    abstract::Novel statistical potentials derived from known protein structures are presented. They are designed to describe cation-pi and amino-pi interactions between a positively charged amino acid or an amino acid carrying a partially charged amino group and an aromatic moiety. These potentials are based on the propensity of r...

    journal_title:Journal of chemical information and modeling

    pub_type: 杂志文章

    doi:10.1021/ci050395b

    authors: Gilis D,Biot C,Buisine E,Dehouck Y,Rooman M

    更新日期:2006-03-01 00:00:00