Abstract:
:A kinetic, reactivity-binding model has been proposed to predict the regioselectivity of substrates meditated by the CYP1A2 enzyme, which is responsible for the metabolism of planar-conjugated compounds such as caffeine. This model consists of a docking simulation for binding energy and a semiempirical molecular orbital calculation for activation energy. Possible binding modes of CYP1A2 substrates were first examined using automated docking based on the crystal structure of CYP1A2, and binding energy was calculated. Then, activation energies for CYP1A2-mediated metabolism reactions were calculated using the semiempirical molecular orbital calculation, AM1. Finally, the metabolic probability obtained from two energy terms, binding and activation energies, was used for predicting the most probable metabolic site. This model predicted 8 out of 12 substrates accurately as the primary preferred site among all possible metabolic sites, and the other four substrates were predicted into the secondary preferred site. This method can be applied for qualitative prediction of drug metabolism mediated by CYP1A2 and other CYP450 family enzymes, helping to develop drugs efficiently.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Jung J,Kim ND,Kim SY,Choi I,Cho KH,Oh WS,Kim DN,No KTdoi
10.1021/ci800001msubject
Has Abstractpub_date
2008-05-01 00:00:00pages
1074-80issue
5eissn
1549-9596issn
1549-960Xjournal_volume
48pub_type
杂志文章abstract::A machine learning enhanced spectrum recognition system called spectrum recognition based on computer vision (SRCV) for data extraction from previously analyzed 13C and 1H NMR spectra has been developed. The intelligent system was designed with four function modules to extract data from three areas of NMR images, incl...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c01046
更新日期:2021-01-25 00:00:00
abstract::Janus kinase 2 (JAK2) is a protein tyrosine kinase implicated in signaling by specific members of the cytokine receptor family. Although it has been established that the JAK2 tyrosine kinase is negatively regulated by the JAK homology 2 (JH2) pseudokinase domain, the underlying mechanism of JH2 mediated regulation rem...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300308g
更新日期:2012-11-26 00:00:00
abstract::Inhibitors of histone deacetylases (HDACIs) have emerged as a new class of drugs for the treatment of human cancers and other diseases because of their effects on cell growth, differentiation, and apoptosis. In this study we have developed several quantitative structure-activity relationship (QSAR) models for 59 chemi...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800366f
更新日期:2009-02-01 00:00:00
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
更新日期:2017-10-23 00:00:00
abstract::Understanding which physicochemical properties, or property distributions, are favorable for successful design and development of drugs, nutritional supplements, cosmetics, and agrochemicals is of great importance. In this study we have analyzed molecules from three distinct chemical spaces (i) approved drugs, (ii) hu...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300487z
更新日期:2013-02-25 00:00:00
abstract::New hits against HIV-1 wild-type and Y181C drug-resistant reverse transcriptases were predicted taking into account the possibility of some of the known metabolism interactions. In silico hits against a set of antitargets (i.e., proteins or nucleic acids that are off-targets from the desired pharmaceutical target obje...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200203h
更新日期:2011-10-24 00:00:00
abstract::Fragment-based methods have emerged in the last two decades as alternatives to traditional high throughput screenings for the identification of chemical starting points in drug discovery. One arguable yet popular assumption about fragment-based design is that the fragment binding mode remains conserved upon chemical e...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300355p
更新日期:2012-12-21 00:00:00
abstract::Big data is one of the key transformative factors which increasingly influences all aspects of modern life. Although this transformation brings vast opportunities it also generates novel challenges, not the least of which is organizing and searching this data deluge. The field of medicinal chemistry is not different: ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00249
更新日期:2017-08-28 00:00:00
abstract::Taking into account dynamical behavior and/or structural inaccuracies of receptor-ligand systems becomes increasingly important in structure-based drug design. Here, we describe the development of consensus Adaptation of Fields for Molecular Comparison (AFMoC) (abbreviated as AFMoCcon) models that account for multiple...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci7002472
更新日期:2007-11-01 00:00:00
abstract::Deep learning has drawn significant attention in different areas including drug discovery. It has been proposed that it could outperform other machine learning algorithms, especially with big data sets. In the field of pharmaceutical industry, machine learning models are built to understand quantitative structure-acti...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00671
更新日期:2019-03-25 00:00:00
abstract::A novel pharmacophore descriptor Flexophore is presented, which considers molecular flexibility when comparing descriptor similarities. The descriptor is a complete reduced graph of the underlying molecule. Its nodes are represented by enhanced MM2 atom types, while the edge descriptions encode the molecular flexibili...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700359j
更新日期:2008-04-01 00:00:00
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
更新日期:2009-03-01 00:00:00
abstract::Accurate and affordable assessment of ligand-protein affinity for structure-based virtual screening (SB-VS) is a standing challenge. Hence, empirical postdocking filters making use of various types of structure-activity information may prove useful. Here, we introduce one such filter based upon three-dimensional struc...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500319f
更新日期:2014-09-22 00:00:00
abstract::We have performed a systematic study of the entropy term in the MM/GBSA (molecular mechanics combined with generalized Born and surface-area solvation) approach to calculate ligand-binding affinities. The entropies are calculated by a normal-mode analysis of harmonic frequencies from minimized snapshots of molecular d...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci3001919
更新日期:2012-08-27 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::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::Cytochrome P450 3A4 metabolizes nearly 50% of the drugs currently in clinical use with a broad range of substrate specificity. Early prediction of metabolites of xenobiotic compounds is crucial for cost efficient drug discovery and development. We developed a new combined model, MLite, for the prediction of regioselec...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci7003576
更新日期:2008-03-01 00:00:00
abstract::The predictive performances of MC4PC were evaluated using its learning machine functionality. Its superior characteristics are demonstrated in this following up study using the newly published Ames mutagenicity benchmark set. ...
journal_title:Journal of chemical information and modeling
pub_type: 评论,信件
doi:10.1021/ci1000899
更新日期:2010-09-27 00:00:00
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
更新日期:2015-10-26 00:00:00
abstract::Aβ25-35 is a short, cytotoxic, and naturally occurring fragment of the Alzheimer's Aβ peptide. To map the molecular mechanism of Aβ25-35 binding to the zwitterionic dimyristoylphosphatidylcholine (DMPC) bilayer, we have performed replica exchange with solute tempering molecular dynamics simulations using all-atom expl...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00045
更新日期:2018-05-29 00:00:00
abstract::Retrieving molecules with specific structural features is a fundamental requirement of today's molecular database technologies. Estimates claim the chemical space relevant for drug discovery to be around 10⁶⁰ molecules. This figure is many orders of magnitude larger than the amount of molecules conventional databases ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400107k
更新日期:2013-07-22 00:00:00
abstract::The yeast protein GCN4 is a transcriptional activator in the basic leucine zipper (bZip) family, whose distinguishing feature is the "chopstick-like" homodimer of alpha helices formed at the DNA-binding interface. While experiments have shown that truncated versions of the protein retain biologically relevant DNA-bind...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500448e
更新日期:2014-10-27 00:00:00
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
更新日期:2013-09-23 00:00:00
abstract::When both the difference between two quantities and their individual values can be measured or computationally predicted, multiple quantities can be determined from the measurements or predictions of select individual quantities and select pairwise differences. These measurements and predictions form a network connect...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00528
更新日期:2019-11-25 00:00:00
abstract::The configuring of a radial basis function network (RBFN) consists of selecting the network parameters (centers and widths in RBF units and weights between the hidden and output layers) and network architecture. The issues of suboptimum and overfitting, however, often occur in RBFN configuring. This paper presented a ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600218d
更新日期:2006-11-01 00:00:00
abstract::The protonation states for nucleic acid bases are difficult to assess experimentally. In the context of DNA triplex, the protonation state of cytidine in the third strand is particularly important, because it needs to be protonated in order to form Hoogsteen hydrogen bonds. A sugar modification, locked nucleic acid (L...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00741
更新日期:2018-04-23 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::Pharmacophore patterns in ligands can be effectively characterized in terms of their constituent pharmacophore multiplets. Bitsets (fingerprints) encoding which particular multiplets are found in a given ligand have been and continue to be used as molecular descriptors in a range of molecular modeling applications, fr...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800234q
更新日期:2008-12-01 00:00:00
abstract::A three-dimensional homology model of the human histamine H 4 receptor was developed to investigate the binding mode of a series of structurally diverse H 4-agonists, i.e. histamine, clozapine, and the recently described selective, nonimidazole agonist VUF 8430. Mutagenesis studies and docking of these ligands in a rh...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700474a
更新日期:2008-07-01 00:00:00
abstract::The binding affinity and relative maximal efficacy of human A3 adenosine receptor (AR) agonists were each subjected to ligand-based three-dimensional quantitative structure-activity relationship analysis. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) used a...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600501z
更新日期:2007-05-01 00:00:00