当前位置： SCI文献检索 > Journal of Chemical Information and Modeling期刊下所有文献 > Flux (2): comparison of molecular mutation and crossover operators for ligand-based de novo design.

Flux (2): comparison of molecular mutation and crossover operators for ligand-based de novo design.

Abstract：

:We implemented a fragment-based de novo design algorithm for a population-based optimization of molecular structures. The concept is grounded on an evolution strategy with mutation and crossover operators for structure breeding. Molecular building blocks were obtained from the pseudo-retrosynthesis of a collection of pharmacologically active compounds following the RECAP principle. The influence of mutation and crossover on the course of optimization was assessed in redesign studies using known drugs as template structures. A topological atom-pair descriptor grounded on potential pharmacophore points was used as a molecular descriptor, and the Manhattan distance between the template and candidate molecules served as a fitness function. Exclusive use of the crossover operator yielded few unique compounds and often resulted in premature convergence of the optimization process, whereas exclusive use of the mutation operator resulted in diverse high-quality structures. Combinations of crossover and mutation yielded the overall best results. The majority of the designed structures exhibit a chemically reasonable architecture; chiral centers are rare, and unfavorable connections of building blocks are infrequent. We conclude that this fragment-based design principle is suited as an idea generator for the automated design of novel leadlike molecules.

journal_name

J Chem Inf Model

journal_title

Journal of chemical information and modeling

authors

Fechner U,Schneider G

doi

10.1021/ci6005307

subject

Has Abstract

pub_date

2007-03-01 00:00:00

pages

656-67

issue

2

eissn

1549-9596

issn

1549-960X

journal_volume

47

pub_type

杂志文章

相关文献

Journal of Chemical Information and Modeling文献大全
  • Computational and conformational evaluation of FTase alternative substrates: insight into a novel enzyme binding pocket.

    abstract：:Protein farnesyltransferase (FTase) is an important anticancer drug target. In an effort to develop isoprenoid diphosphate-based FTase inhibitors, striking variations have been observed in the ability of conservatively modified analogues to bind to the enzyme. For example, 2Z-GGPP is an alternative substrate with high...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci0496550

    authors： Henriksen BS,Zahn TJ,Evanseck JD,Firestine SM,Gibbs RA

    更新日期：2005-07-01 00:00:00

  • Structural basis for the mutation-induced dysfunction of human CYP2J2: a computational study.

    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...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci400003p

    authors： Cong S,Ma XT,Li YX,Wang JF

    更新日期：2013-06-24 00:00:00

  • Time-Domain Analysis of Molecular Dynamics Trajectories Using Deep Neural Networks: Application to Activity Ranking of Tankyrase Inhibitors.

    abstract：:Molecular dynamics simulations provide valuable insights into the behavior of molecular systems. Extending the recent trend of using machine learning techniques to predict physicochemical properties from molecular dynamics data, we propose to consider the trajectories as multidimensional time series represented by 2D ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.9b00135

    authors： Berishvili VP,Perkin VO,Voronkov AE,Radchenko EV,Syed R,Venkata Ramana Reddy C,Pillay V,Kumar P,Choonara YE,Kamal A,Palyulin VA

    更新日期：2019-08-26 00:00:00

  • Reliable and Performant Identification of Low-Energy Conformers in the Gas Phase and Water.

    abstract：:Prediction of compound properties from structure via quantitative structure-activity relationship and machine-learning approaches is an important computational chemistry task in small-molecule drug research. Though many such properties are dependent on three-dimensional structures or even conformer ensembles, the majo...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00151

    authors： Cavasin AT,Hillisch A,Uellendahl F,Schneckener S,Göller AH

    更新日期：2018-05-29 00:00:00

  • Criterion for evaluating the predictive ability of nonlinear regression models without cross-validation.

    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

    authors： Kaneko H,Funatsu K

    更新日期：2013-09-23 00:00:00

  • Enrichment analysis for discovering biological associations in phenotypic screens.

    abstract：:A phenotypic screen (PS) is used to identify compounds causing a desired phenotype in a complex biological system where mechanisms and targets are largely unknown. Deconvoluting the mechanism of action of actives and identification of relevant targets and pathways remains a formidable challenge. Current methods fail t...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci400245c

    authors： Polyakov VR,Moorcroft ND,Drawid A

    更新日期：2014-02-24 00:00:00

  • Two model system of the alpha1A-adrenoceptor docked with selected ligands.

    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-methylur...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci700026v

    authors： Asher WB,Hoskins SN,Slasor LA,Morris DH,Cook EM,Bautista DL

    更新日期：2007-09-01 00:00:00

  • Matched Molecular Series Analysis for ADME Property Prediction.

    abstract：:Generation and prioritization of new molecules are the most central part of the drug design process. Matched molecular series analysis (MMSA) has recently been proposed as a formal approach that captures both of these key elements of design. In order to better understand the power of MMSA and its specific limitations,...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.0c00269

    authors： Awale M,Riniker S,Kramer C

    更新日期：2020-06-22 00:00:00

  • Pharmacophore-based virtual screening and experimental validation of novel inhibitors against cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphosphatase.

    abstract：:Cyanobacterial fructose-1,6-/sedoheptulose-1,7-bisphoshatase (cy-FBP/SBPase) is a potential enzymatic target for screening of novel inhibitors that can combat harmful algal blooms. In the present study, we targeted the substrate binding pocket of cy-FBP/SBPase. A series of novel hit compounds from the SPECs database w...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci4007529

    authors： Sun Y,Zhang R,Li D,Feng L,Wu D,Feng L,Huang P,Ren Y,Feng J,Xiao S,Wan J

    更新日期：2014-03-24 00:00:00

  • RED: a set of molecular descriptors based on Renyi entropy.

    abstract：:New molecular descriptors, RED (Renyi entropy descriptors), based on the generalized entropies introduced by Renyi are presented. Topological descriptors based on molecular features have proven to be useful for describing molecular profiles. Renyi entropy is used as a variability measure to contract a feature-pair dis...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci900275w

    authors： Delgado-Soler L,Toral R,Tomás MS,Rubio-Martinez J

    更新日期：2009-11-01 00:00:00

  • OPUS-Rota3: Improving Protein Side-Chain Modeling by Deep Neural Networks and Ensemble Methods.

    abstract：:Side-chain modeling is critical for protein structure prediction since the uniqueness of the protein structure is largely determined by its side-chain packing conformation. In this paper, differing from most approaches that rely on rotamer library sampling, we first propose a novel side-chain rotamer prediction method...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.0c00951

    authors： Xu G,Wang Q,Ma J

    更新日期：2020-12-28 00:00:00

  • Receptor-based virtual ligand screening for the identification of novel CDC25 phosphatase inhibitors.

    abstract：:CDC25 phosphatases play critical roles in cell cycle regulation and are attractive targets for anticancer therapies. Several small non-peptide molecules are known to inhibit CDC25, but many of them appear to form a covalent bond with the enzyme or act through oxidation of the thiolate group of the catalytic cysteine. ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci700313e

    authors： Montes M,Braud E,Miteva MA,Goddard ML,Mondésert O,Kolb S,Brun MP,Ducommun B,Garbay C,Villoutreix BO

    更新日期：2008-01-01 00:00:00

  • Free energy calculations give insight into the stereoselective hydroxylation of α-ionones by engineered cytochrome P450 BM3 mutants.

    abstract：:Previously, stereoselective hydroxylation of α-ionone by Cytochrome P450 BM3 mutants M01 A82W and M11 L437N was observed. While both mutants hydroxylate α-ionone in a regioselective manner at the C3 position, M01 A82W catalyzes formation of trans-3-OH-α-ionone products whereas M11 L437N exhibits opposite stereoselecti...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci300243n

    authors： de Beer SB,Venkataraman H,Geerke DP,Oostenbrink C,Vermeulen NP

    更新日期：2012-08-27 00:00:00

  • Getting Docking into Shape Using Negative Image-Based Rescoring.

    abstract：:The failure of default scoring functions to ensure virtual screening enrichment is a persistent problem for the molecular docking algorithms used in structure-based drug discovery. To remedy this problem, elaborate rescoring and postprocessing schemes have been developed with a varying degree of success, specificity, ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.9b00383

    authors： Kurkinen ST,Lätti S,Pentikäinen OT,Postila PA

    更新日期：2019-08-26 00:00:00

  • Rapid evaluation of synthetic and molecular complexity for in silico chemistry.

    abstract：:Methods that rapidly evaluate molecular complexity and synthetic feasibility are becoming increasingly important for in silico chemistry. We propose a new metric based on relative atomic electronegativities and bond parameters that evaluate both synthetic and molecular complexity (SMCM) starting from chemical structur...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci0501387

    authors： Allu TK,Oprea TI

    更新日期：2005-09-01 00:00:00

  • Multiple e-pharmacophore modeling, 3D-QSAR, and high-throughput virtual screening of hepatitis C virus NS5B polymerase inhibitors.

    abstract：:The hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRP) is a crucial and unique component of the HCV RNA replication machinery and a validated target for drug discovery. Multiple crystal structures of NS5B inhibitor complexes have facilitated the identification of novel compound scaffolds through in silic...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci400644r

    authors： Therese PJ,Manvar D,Kondepudi S,Battu MB,Sriram D,Basu A,Yogeeswari P,Kaushik-Basu N

    更新日期：2014-02-24 00:00:00

  • QM/MM calculations in drug discovery: a useful method for studying binding phenomena?

    abstract：:Herein we investigate whether QM/MM could prove useful as a tool to study the often subtle binding phenomena found within pharmaceutical drug discovery programs. The goal of this investigation is to determine whether it is possible to employ high level QM/MM calculations to answer specific questions around a binding e...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci800419j

    authors： Gleeson MP,Gleeson D

    更新日期：2009-03-01 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

  • Unraveling Energy and Dynamics Determinants to Interpret Protein Functional Plasticity: The Limonene-1,2-epoxide-hydrolase Case Study.

    abstract：:The balance between structural stability and functional plasticity in proteins that share common three-dimensional folds is the key factor that drives protein evolvability. The ability to distinguish the parts of homologous proteins that underlie common structural organization patterns from the parts acting as regulat...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.6b00504

    authors： Rinaldi S,Gori A,Annovazzi C,Ferrandi EE,Monti D,Colombo G

    更新日期：2017-04-24 00:00:00

  • Heuristics from Modeling of Spectral Overlap in Förster Resonance Energy Transfer (FRET).

    abstract：:Among the photophysical parameters that underpin Förster resonance energy transfer (FRET), perhaps the least explored is the spectral overlap term ( J). While by definition J increases linearly with acceptor molar absorption coefficient (ε(A) in M-1 cm-1), is proportional to wavelength (λ4), and depends on the degree ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00753

    authors： Qi Q,Taniguchi M,Lindsey JS

    更新日期：2019-02-25 00:00:00

  • Enrichment factor analyses on G-protein coupled receptors with known crystal structure.

    abstract：:G-protein coupled receptors (GPCRs) are highly relevant drug targets. Four GPCRs with known crystal structure were analyzed with docking (AutoDock4) and postdocking (MM-PBSA) in order to evaluate the ability to recognize known antagonists from a larger database of molecular decoys and to predict correct binding modes....

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci4000745

    authors： Anighoro A,Rastelli G

    更新日期：2013-04-22 00:00:00

  • Building Graphs To Describe Dynamics, Kinetics, and Energetics in the d-ALa:d-Lac Ligase VanA.

    abstract：:The d-Ala:d-Lac ligase, VanA, plays a critical role in the resistance of vancomycin. Indeed, it is involved in the synthesis of a peptidoglycan precursor, to which vancomycin cannot bind. The reaction catalyzed by VanA requires the opening of the so-called "ω-loop", so that the substrates can enter the active site. He...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.6b00211

    authors： Duclert-Savatier N,Bouvier G,Nilges M,Malliavin TE

    更新日期：2016-09-26 00:00:00

  • FragPELE: Dynamic Ligand Growing within a Binding Site. A Novel Tool for Hit-To-Lead Drug Design.

    abstract：:The early stages of drug discovery rely on hit-to-lead programs, where initial hits undergo partial optimization to improve binding affinities for their biological target. This is an expensive and time-consuming process, requiring multiple iterations of trial and error designs, an ideal scenario for applying computer ...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.9b00938

    authors： Perez C,Soler D,Soliva R,Guallar V

    更新日期：2020-03-23 00:00:00

  • ColBioS-FlavRC: a collection of bioselective flavonoids and related compounds filtered from high-throughput screening outcomes.

    abstract：:Flavonoids, the vastest class of natural polyphenols, are extensively investigated for their multiple benefits on human health. Due to their physicochemical or biological properties, many representatives are considered to exhibit low selectivity among various protein targets or to plague high-throughput screening (HTS...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci5002668

    authors： Avram SI,Pacureanu LM,Bora A,Crisan L,Avram S,Kurunczi L

    更新日期：2014-08-25 00:00:00

  • Efficient Corrections for DFT Noncovalent Interactions Based on Ensemble Learning Models.

    abstract：:Machine learning has exhibited powerful capabilities in many areas. However, machine learning models are mostly database dependent, requiring a new model if the database changes. Therefore, a universal model is highly desired to accommodate the widest variety of databases. Fortunately, this universality may be achieve...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.8b00878

    authors： Li W,Miao W,Cui J,Fang C,Su S,Li H,Hu L,Lu Y,Chen G

    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

  • Effect of structural stress on the flexibility and adaptability of HIV-1 protease.

    abstract：:Resistance remains a major issue with regards to HIV-1 protease, despite the availability of numerous HIV-1 protease inhibitors and copious amounts of structural and binding data. In an effort to improve our understanding of how HIV-1 protease is able to "outsmart" new drugs, we have investigated the flexibility of HI...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci2000677

    authors： Oehme DP,Wilson DJ,Brownlee RT

    更新日期：2011-05-23 00:00:00

  • Identification of novel potential antibiotics against Staphylococcus using structure-based drug screening targeting dihydrofolate reductase.

    abstract：:The emergence of multidrug-resistant Staphylococcus aureus (S. aureus) makes the treatment of infectious diseases in hospitals more difficult and increases the mortality of the patients. In this study, we attempted to identify novel potent antibiotic candidate compounds against S. aureus dihydrofolate reductase (saDHF...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci400686d

    authors： Kobayashi M,Kinjo T,Koseki Y,Bourne CR,Barrow WW,Aoki S

    更新日期：2014-04-28 00:00:00

  • Evaluation and Characterization of Trk Kinase Inhibitors for the Treatment of Pain: Reliable Binding Affinity Predictions from Theory and Computation.

    abstract：:Optimization of ligand binding affinity to the target protein of interest is a primary objective in small-molecule drug discovery. Until now, the prediction of binding affinities by computational methods has not been widely applied in the drug discovery process, mainly because of its lack of accuracy and reproducibili...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/acs.jcim.6b00780

    authors： Wan S,Bhati AP,Skerratt S,Omoto K,Shanmugasundaram V,Bagal SK,Coveney PV

    更新日期：2017-04-24 00:00:00

  • Protein structural statistics with PSS.

    abstract：:Characterizing the variability within an ensemble of protein structures is a common requirement in structural biology and bioinformatics. With the increasing number of protein structures becoming available, there is a need for new tools capable of automating the structural comparison of large ensemble of structures. W...

    journal_title：Journal of chemical information and modeling

    pub_type： 杂志文章

    doi：10.1021/ci400233j

    authors： Gaillard T,Schwarz BB,Chebaro Y,Stote RH,Dejaegere A

    更新日期：2013-09-23 00:00:00