Abstract：
:In this work, we present molecular modeling studies carried out using six DNA sequences and six azinomycin analogues, including the naturally occurring compound azinomycin B, selected on the basis of known cell cytotoxicity and structural analogies (epoxide and aziridine alkylating moieties). Among several computational methods the Stochastic Dynamics with Energy Minimization (SDEM) approach yielded results superior to the others with the natural compound (r(2) > 0.9) and was adopted for studying other DNA adducts, obtaining good correlation between the average theoretical cross-linking properties and the antitumor activity scale. As a result, some interesting SAR considerations have been highlighted and a cross-linking conformation different from that of the azinomycin was identified in a less potent, simplified analogue.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Alcaro S,Ortuso F,Coleman RSdoi
10.1021/ci0496595keywords:
subject
Has Abstractpub_date
2005-05-01 00:00:00pages
602-9issue
3eissn
1549-9596issn
1549-960Xjournal_volume
45pub_type
杂志文章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
更新日期：2006-03-01 00:00:00
abstract：:We propose a hypothesis that "a model of active compound can be provided by integrating information of compounds high-ranked by docking simulation of a random compound library". In our hypothesis, the inclusion of true active compounds in the high-ranked compound is not necessary. We regard the high-ranked compounds a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci7003384
更新日期：2008-03-01 00:00:00
abstract：:Piperine, the bioactive phytochemical from black pepper (Piper nigrum L.), is a nontoxic natural compound exhibiting many physiological and pharmacological properties. They include antioxidant, anti-inflammatory, antimutagenic, antitumor, antiapoptotic, antigenotoxic, antiarthritic, antifungal, antimicrobial, antidepr...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00514
更新日期：2015-12-28 00:00:00
abstract：:The SZMAP method computes binding free energies and the corresponding thermodynamic components for water molecules in the binding site of a protein structure [ SZMAP, 1.0.0 ; OpenEye Scientific Software Inc. : Santa Fe, NM, USA , 2011 ]. In this work, the ability of SZMAP to predict water structure and thermodynamic s...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500746d
更新日期：2015-08-24 00:00:00
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
更新日期：2014-02-24 00:00:00
abstract：:In this study, two probabilistic machine-learning algorithms were compared for in silico target prediction of bioactive molecules, namely the well-established Laplacian-modified Naïve Bayes classifier (NB) and the more recently introduced (to Cheminformatics) Parzen-Rosenblatt Window. Both classifiers were trained in ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300435j
更新日期：2013-08-26 00:00:00
abstract：:Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in the market against cancer until date. Computer-based or in silico virtual screening methods are often used in lead/hit discovery protocols. In this study, the "drug-likeness" of ~400 compounds from Africa...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5003697
更新日期：2014-09-22 00:00:00
abstract：:The prediction of protein-ligand binding affinity has recently been improved remarkably by machine-learning-based scoring functions. For example, using a set of simple descriptors representing the atomic distance counts, the RF-Score improves the Pearson correlation coefficient to about 0.8 on the core set of the PDBb...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00049
更新日期：2017-04-24 00:00:00
abstract：:Binding affinity prediction with implicit solvent models remains a challenge in virtual screening for drug discovery. In order to assess the predictive power of implicit solvent models in docking techniques with Amber scoring, three generalized Born models (GBHCT, GBOBCI, and GBOBCII) available in Dock 6.7 were utiliz...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00418
更新日期：2016-10-24 00:00:00
abstract：:Drug-induced torsade de pointes (TdP) is a life-threatening ventricular arrhythmia responsible for the withdrawal of many drugs from the market. Although currently used TdP risk-assessment methods are effective, they are expensive and prone to produce false positives. In recent years, in silico cardiac simulations hav...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00201
更新日期：2020-10-26 00:00:00
abstract：:Serotonin 5-HT6 receptor antagonists are thought to play an important role in the treatment of psychiatry, Alzheimer's disease, and probably obesity. To find novel and potent 5-HT6 antagonists and to provide a new idea for drug design, we used a ligand-based pharmacophore to perform the virtual screening of a commerci...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700160t
更新日期：2008-01-01 00:00:00
abstract：:Protein-ligand binding is essential to almost all life processes. The understanding of protein-ligand interactions is fundamentally important to rational drug and protein design. Based on large scale data sets, we show that protein rigidity strengthening or flexibility reduction is a mechanism in protein-ligand bindin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00226
更新日期：2017-07-24 00:00:00
abstract：:The important role of water molecules in protein-ligand binding energetics has attracted wide attention in recent years. A range of computational methods has been developed to predict the favorable locations of water molecules in a protein binding pocket. Most of the current methods are based on extensive molecular dy...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00619
更新日期：2020-09-28 00:00:00
abstract：:A comprehensive data set of aligned ligands with highly similar binding pockets from the Protein Data Bank has been built. Based on this data set, a scoring function for recognizing good alignment poses for small molecules has been developed. This function is based on atoms and hydrogen-bond projected features. The co...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100227h
更新日期：2010-09-27 00:00:00
abstract：:With chemical libraries increasingly containing millions of compounds or more, there is a fast-growing need for computational methods that can rank or prioritize compounds for screening. Machine learning methods have shown considerable promise for this task; indeed, classification methods such as support vector machin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9003865
更新日期：2010-05-24 00:00:00
abstract：:The conformational properties of AT1 antagonist valsartan have been analyzed both in solution and at the binding site of the receptor. Low energy conformations of valsartan in solution were explored by NMR spectroscopy and molecular modeling studies. The NMR results showed the existence of two distinct and almost isoe...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800427s
更新日期：2009-03-01 00:00:00
abstract：:Factor Xa inhibitors are innovative anticoagulant agents that provide a better safety/efficacy profile compared to other anticoagulative drugs. A chemical feature-based modeling approach was applied to identify crucial pharmacophore patterns from 3D crystal structures of inhibitors bound to human factor Xa (Pdb entrie...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci049778k
更新日期：2005-01-01 00:00:00
abstract：:The interaction between small molecules and proteins is one of the major concerns for structure-based drug design because the principles of protein-ligand interactions and molecular recognition are not thoroughly understood. Fortunately, the analysis of protein-ligand complexes in the Protein Data Bank (PDB) enables u...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100386y
更新日期：2011-04-25 00:00:00
abstract：:Binding hot spots are regions of proteins that, due to their potentially high contribution to the binding free energy, have high propensity to bind small molecules. We present benchmark sets for testing computational methods for the identification of binding hot spots with emphasis on fragment-based ligand discovery. ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00877
更新日期：2020-12-28 00:00:00
abstract：:A new methodology to describe the interactions in "receptor-ligand" complexes is presented. The methodology is based on a combination of the 3D/4D QSAR BiS/MC and CoCon algorithms. The first algorithm performs the restricted docking of compounds to receptor pockets. The second determines the relationships between the ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800405n
更新日期：2009-06-01 00:00:00
abstract：:Membrane transporters play a crucial role in determining fate of administered drugs in a biological system. Early identification of plausible transporters for a drug molecule can provide insights into its therapeutic, pharmacokinetic, and toxicological profiles. In the present study, predictive models for classifying ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00508
更新日期：2017-03-27 00:00:00
abstract：:Acetohydroxyacid synthase (AHAS) is a thiamin diphosphate-dependent enzyme involved in the biosynthesis of valine, leucine, isoleucine, and lysine. Experimental evidence has shown that mutation of the Gln202 residue results in a decrease in the enzymatic activity, thus suggesting the main role of the carboligation cat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00863
更新日期：2020-02-24 00:00:00
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
更新日期：2019-02-25 00:00:00
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
更新日期：2014-04-28 00:00:00
abstract：:Target-oriented substructure-based virtual screening (sSBVS) of molecules is a promising approach in drug discovery. Yet, there are doubts whether sSBVS is suitable also for extrapolation, that is, for detecting molecules that are very different from those used for training. Herein, we evaluate the predictive power of...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200472s
更新日期：2012-03-26 00:00:00
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
更新日期：2019-08-26 00:00:00
abstract：:Large corpora of kinase small molecule inhibitor data are accessible to public sector research from thousands of journal article and patent publications. These data have been generated employing a wide variety of assay methodologies and experimental procedures by numerous laboratories. Here we ask the question how app...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300403k
更新日期：2013-01-28 00:00:00
abstract：:Several hypotheses to elucidate the linkage isomer preference of the thiocyanate (SCN(-)) ion have been offered. For complexes with small coordination numbers (i.e., 1 and 2) and groups 11 (Cu-triad) and 12 (Zn-triad) metals, different levels of theory and a variety of basis sets have been employed to study linkage is...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050050t
更新日期：2005-07-01 00:00:00
abstract：:Little attention has been given to the selection of trial descriptor sets when designing a QSAR analysis even though a great number of descriptor classes, and often a greater number of descriptors within a given class, are now available. This paper reports an effort to explore interrelationships between QSAR models an...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci3005308
更新日期：2013-01-28 00:00:00
abstract：:There are only four derivatives of pseudouridine (Ψ) that are known to occur naturally in RNA as post-transcriptional modifications. We have studied the conformational consequences of pseudouridylation and further modifications using replica exchange molecular dynamics simulations at the nucleoside level, and the simu...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00369
更新日期：2020-10-26 00:00:00
