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. Structure-based virtual ligand screening computations were performed with FRED, Surflex, and LigandFit, a compound collection of over 310,000 druglike molecules and the crystal structure of CDC25B in order to identify novel classes of ligands. In vitro experiments carried out on a selected list of 1500 molecules led to the discovery of 99 compounds able to inhibit CDC25B activity at 100 microM. Further docking computations were applied, allowing us to propose a binding mode for the most potent molecule (IC50 = 13 microM). Our best compounds represent promising new classes of CDC25 inhibitors that also exhibit antiproliferative properties.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Montes M,Braud E,Miteva MA,Goddard ML,Mondésert O,Kolb S,Brun MP,Ducommun B,Garbay C,Villoutreix BOdoi
10.1021/ci700313esubject
Has Abstractpub_date
2008-01-01 00:00:00pages
157-65issue
1eissn
1549-9596issn
1549-960Xjournal_volume
48pub_type
杂志文章abstract：:Calcium and magnesium ions play important roles in many physicochemical processes. To facilitate the investigation of phenomena related to these ions that occur over large length and time scales, a coarse-grained force field (CGFF) is developed for MgCl2 and CaCl2 aqueous solutions. The ions are modeled by CG beads wi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00206
更新日期：2017-07-24 00:00:00
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 w...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700428d
更新日期：2008-03-01 00:00:00
abstract：:Due to the importance of hot-spots (HS) detection and the efficiency of computational methodologies, several HS detecting approaches have been developed. The current paper presents new models to predict HS for protein-protein and protein-nucleic acid interactions with better statistics compared with the ones currently...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500760m
更新日期：2015-05-26 00:00:00
abstract：:The present study focuses on the determination of the biologically significant N-acetylneuraminic acid (NANA) drug binding interaction mechanism between bovine serum albumin (BSA) and human α-1 acid glycoprotein (HAG) using various optical spectroscopy and computational methods. The steady state fluorescence spectrosc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00558
更新日期：2019-01-28 00:00:00
abstract：:We used synthetic peloruside A for the commercial preparation of [³H]peloruside A. The radiolabeled compound bound to preformed tubulin polymer in amounts stoichiometric with the polymer's tubulin content, with an apparent K(d) value of 0.35 μM. A less active peloruside A analogue, (11-R)-peloruside A and laulimalide ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci1002894
更新日期：2010-11-22 00:00:00
abstract：:The second extracellular loops (ECL2s) of G-protein-coupled receptors (GPCRs) are often involved in GPCR functions, and their structures have important implications in drug discovery. However, structure prediction of ECL2 is difficult because of its long length and the structural diversity among different GPCRs. In th...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00148
更新日期：2018-06-25 00:00:00
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
更新日期：2012-10-22 00:00:00
abstract：:The accurate prediction of the adsorption energies of unsaturated molecules on graphene in the presence of water is essential for the design of molecules that can modify its properties and that can aid its processability. We here show that a semiempirical MO method corrected for dispersive interactions (PM6-DH2) can p...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5003729
更新日期：2014-08-25 00:00:00
abstract：:The COSMO surface polarization charge density σ resulting from quantum chemical calculations combined with a virtual conductor embedding has been widely proven to be a very suitable descriptor for the quantification of interactions of molecules in liquids. In a preceding paper, grid-based local histograms of σ have be...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300231t
更新日期：2012-08-27 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：:Targeted covalent inhibitors (TCIs) have been successfully developed as high-affinity and selective inhibitors of enzymes of the protein kinase family. These drugs typically act by undergoing an electrophilic addition with an active-site cysteine residue, so design of a TCI begins with the identification of a "druggab...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00454
更新日期：2018-09-24 00:00:00
abstract：:Moving to a new country, with a different culture and a new environment, is not an easy decision. In this perspective, I present some reasons that made me, a Brazilian computational biochemist, move abroad to do postdoctoral research and some of the challenges I faced before and after moving. ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00764
更新日期：2020-02-24 00:00:00
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
更新日期：2018-10-22 00:00:00
abstract：:In this paper, we introduce the BiKi Life Sciences suite. This software makes it easy for computational medicinal chemists to run ad hoc molecular dynamics protocols in a novel and task-oriented environment; as a notebook, BiKi (acronym of Binding Kinetics) keeps memory of any activity together with dependencies among...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00680
更新日期：2018-02-26 00:00:00
abstract：:Fragment complementation is gaining an increasing impact as a nonperturbing method to probe noncovalent interactions within protein supersecondary structures. In this study, the fast Fourier transform rigid-body docking algorithm ZDOCK has been employed for in silico reconstitution of the calcium binding protein calbi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0501995
更新日期：2005-09-01 00:00:00
abstract：:HackaMol is an open source, object-oriented toolkit written in Modern Perl that organizes atoms within molecules and provides chemically intuitive attributes and methods. The library consists of two components: HackaMol, the core that contains classes for storing and manipulating molecular information, and HackaMol::X...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500359e
更新日期：2015-04-27 00:00:00
abstract：:The consistent handling of molecules is probably the most basic and important requirement in the field of cheminformatics. Reliable results can only be obtained if the underlying calculations are independent of the specific way molecules are represented in the input data. However, ensuring consistency is a complex tas...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400724v
更新日期：2014-03-24 00:00:00
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
更新日期：2019-03-25 00:00:00
abstract：:Physicochemical atomic stereodescriptors (PAS) were implemented that represent the chirality of an atomic chiral center on the basis of empirical physicochemical properties of the ligands. The ligands are ranked according to a specific property, and the chiral center takes an S/R-like descriptor relative to that prope...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600235w
更新日期：2006-11-01 00:00:00
abstract：:The viral NS5B RNA-dependent RNA-polymerase (RdRp) is one of the best-studied and promising targets for the development of novel therapeutics against hepatitis C virus (HCV). Allosteric inhibition of this enzyme has emerged as a viable strategy toward blocking replication of viral RNA in cell based systems. Herein, we...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9004749
更新日期：2010-04-26 00:00:00
abstract：:The reuptake of neurotransmitters by dopamine, norepinephrine, and serotonin transporters during neuronal transmission requires a sodium gradient. An "ionic mode" of binding proposes that aspartate anchors the ligand's positive charge but ignores the direct role of sodium in ligand binding seen in the only representat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700255d
更新日期：2008-07-01 00:00:00
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
更新日期：2014-12-22 00:00:00
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
更新日期：2014-01-27 00:00:00
abstract：:Support vector regression (SVR) is a premier approach for the prediction of compound potency. Given the conceptual link between support vector machine (SVM) and SVR modeling, SVR is capable of accounting for continuous and discontinuous structure-activity relationships (SARs) in potency prediction, which further exten...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00584
更新日期：2019-03-25 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：:The roles of chemical compounds in biological systems are now systematically analyzed by high-throughput experimental technologies. To automate the processing and interpretation of large-scale data it is necessary to develop bioinformatics methods to extract information from the chemical structures of these small mole...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700006f
更新日期：2007-07-01 00:00:00
abstract：:This article presents the computation of both inter- and intramolecular hydrogen bond strengths from first-principles. Quantum chemical calculations conducted at the dispersion-corrected density functional theory level including free energy and solvation contributions are conducted for (i) one-to-one hydrogen-bonded c...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00132
更新日期：2019-09-23 00:00:00
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
更新日期：2021-01-25 00:00:00
abstract：:Soluble low-molecular-weight oligomers formed during the early stage of amyloid aggregation are considered the major toxic species in amyloidosis. The structure-function relationship between oligomeric assemblies and the cytotoxicity in amyloid diseases are still elusive due to the heterogeneous and transient nature o...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c01319
更新日期：2021-01-14 00:00:00
abstract：:The chronic toxicity is fundamental for toxicological risk assessment, but its correlation with the chemical structures has been studied only little. This is partly due to the complexity of such an experimental test that embraces a plethora of different biological effects and mechanisms of action, making (Q)SAR studie...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci8001974
更新日期：2008-10-01 00:00:00
