Abstract:
:Reactive oxygen species such as superoxide are potentially harmful byproducts of the aerobic metabolism in the inner mitochondrial membrane, and complexes I, II, III of the electron transport chain have been identified as primary sources. The mitochondrial fatty acid b-oxidation pathway may also play a yet uncharacterized role in reactive oxygen species generation, apparently at the level of the electron transfer flavoprotein:ubiquinone oxidoreductase (ETF:QO) and/or its redox partner electron-transfer flavoprotein (ETF). These enzymes comprise a key pathway through which electrons are sequentially shuttled from several dehydrogenases to the respiratory chain. The exact mechanisms of superoxide production have not been fully established, but a crucial starting point would be the binding of molecular oxygen within one of the protein complexes. The present investigation offers a comprehensive computational approach for the determination of binding modes and characteristic binding times of small molecules inside proteins, which is then used to reveal several O2 binding sites near the flavin adenine dinucleotide cofactor of the ETF enzyme. The binding sites are further characterized to extract the necessary parameters for further studies of possible electron transfer between flavin and O2 leading to radical pair formation and possible superoxide production.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Husen P,Nielsen C,Martino CF,Solov'yov IAdoi
10.1021/acs.jcim.9b00702subject
Has Abstractpub_date
2019-11-25 00:00:00pages
4868-4879issue
11eissn
1549-9596issn
1549-960Xjournal_volume
59pub_type
杂志文章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::The knowledge of the capacity of a data set to be modeled in the first stages of the building of quantitative structure-activity relationship (QSAR) prediction models is an important issue because it might reduce the effort and time necessary to select or reject data sets and in refining the data set's composition. Th...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00188
更新日期:2018-09-24 00:00:00
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::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
更新日期:2017-04-24 00:00:00
abstract::The industrial production of higher-generation semisynthetic cephalosporins starts from 7-aminocephalosporanic acid (7-ACA), which is obtained by deacylation of the naturally occurring antibiotic cephalosporin C (CephC). The enzymatic process in which CephC is directly converted into 7-ACA by a cephalosporin C acylase...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00535
更新日期:2015-10-26 00:00:00
abstract::The purpose of this investigation is to contribute to the development of new anticonvulsant drugs to treat patients with refractory epilepsy. We applied a virtual screening protocol that involved the search into molecular databases of new compounds and known drugs to find small molecules that interact with the open co...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00721
更新日期:2018-07-23 00:00:00
abstract::We describe a novel deep learning neural network method and its application to impute assay pIC50 values. Unlike conventional machine learning approaches, this method is trained on sparse bioactivity data as input, typical of that found in public and commercial databases, enabling it to learn directly from correlation...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00768
更新日期:2019-03-25 00:00:00
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
更新日期:2017-04-24 00:00:00
abstract::Several drugs elicit their therapeutic efficacy by modulating multiple cellular targets and possess varied polypharmacological actions. The identification of the molecular targets of a potent bioactive molecule is essential in determining its overall polypharmacological profile. Experimental procedures are expensive a...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00227
更新日期:2018-01-22 00:00:00
abstract::Protein-ligand (PL) interactions play a key role in many life processes such as molecular recognition, molecular binding, signal transmission, and cell metabolism. Examples of interaction forces include hydrogen bonding, hydrophobic effects, steric clashes, electrostatic contacts, and van der Waals attractions. Curren...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00310
更新日期:2018-01-22 00:00:00
abstract::Nonalcoholic hepatic steatosis is a worldwide epidemiological concern since it is among the most prominent hepatic diseases. Indeed, research in toxicology and epidemiology has gathered evidence that exposure to endocrine disruptors can perturb cellular homeostasis and cause this disease. Therefore, assessing the like...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00297
更新日期:2018-08-27 00:00:00
abstract::QSPR studies, using scores of SciTegic's extended connectivity fingerprint as raw descriptors, were extended to the prediction of melting points and aqueous solubility of organic compounds. Robust partial least-squares models were developed that perform as well as the best published QSPR models for structurally divers...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800024c
更新日期:2008-05-01 00:00:00
abstract::Predictive metabolism methods can be used in drug discovery projects to enhance the understanding of structure-metabolism relationships. The present study uses data mining methods to exploit biotransformation data that have been recorded in the MDL Metabolite database. Reacting center fingerprints were derived from a ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600376q
更新日期:2007-03-01 00:00:00
abstract::Understanding the relationship between chemical structure and function is a ubiquitous problem within the fields of chemistry and biology. Simulation approaches attack the problem utilizing physics to understand a given process at the particle level. Unfortunately, these approaches are often too expensive for many pro...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci8001233
更新日期:2008-08-01 00:00:00
abstract::Given the need for modern researchers to produce open, reproducible scientific output, the lack of standards and best practices for sharing data and workflows used to produce and analyze molecular dynamics (MD) simulations has become an important issue in the field. There are now multiple well-established packages to ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00665
更新日期:2019-10-28 00:00:00
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
更新日期:2019-08-26 00:00:00
abstract::Proteins often have both orthosteric and allosteric binding sites. Endogenous ligands, such as hormones and neurotransmitters, bind to the orthosteric site, while synthetic ligands may bind to orthosteric or allosteric sites, which has become a focal point in drug discovery. Usually, such allosteric modulators bind to...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00695
更新日期:2020-10-26 00:00:00
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
更新日期:2009-11-01 00:00:00
abstract::It is of great interest in modern drug design to accurately calculate the free energies of protein-ligand or nucleic acid-ligand binding. MM-PBSA (molecular mechanics Poisson-Boltzmann surface area) and MM-GBSA (molecular mechanics generalized Born surface area) have gained popularity in this field. For both methods, ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300064d
更新日期:2012-05-25 00:00:00
abstract::Calcium is involved in important intracellular processes, such as intracellular signaling from cell membrane receptors to the nucleus. Typically, calcium levels are kept at less than 100 nM in the nucleus and cytosol, but some calcium is stored in the endoplasmic reticulum (ER) lumen for rapid release to activate intr...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00475
更新日期:2017-02-27 00:00:00
abstract::Molecular channel exploration perseveres to be the prominent solution for eliciting structure and accessibility of active site and other internal spaces of macromolecules. The volume and silhouette characterization of these channels provides answers for the issues of substrate access and ligand swapping between the ob...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200584f
更新日期:2012-02-27 00:00:00
abstract::Metabolic stability is an important property of drug molecules that should-optimally-be taken into account early on in the drug design process. Along with numerous medium- or high-throughput assays being implemented in early drug discovery, a prediction tool for this property could be of high value. However, metabolic...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700142c
更新日期:2008-04-01 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::Homology modeling is a reliable method of predicting the three-dimensional structures of proteins that lack NMR or X-ray crystallographic data. It employs the assumption that a structural resemblance exists between closely related proteins. Despite the availability of many crystal structures of possible templates, onl...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500001f
更新日期:2014-06-23 00:00:00
abstract::Knowledge of the interactions between drugs and transporters is important for drug discovery and development as well as for the evaluation of their clinical safety. We recently developed a text-mining system for the automatic extraction of information on chemical-CYP3A4 interactions from the literature. This system is...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci4003188
更新日期:2013-10-28 00:00:00
abstract::Mass spectrometric data are copious and generate a processing burden that is best dealt with programmatically. PythoMS is a collection of tools based on the Python programming language that assist researchers in creating figures and video output that is informative, clear, and visually compelling. The PythoMS framewor...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00055
更新日期:2019-04-22 00:00:00
abstract::LEAFY (LFY) is a plant-specific transcription factor, with a variety of roles in different species. LFY contains a conserved DNA-binding domain (DBD) that determines its DNA-binding specificity. Recently, the structures of the dimeric LFY-DBD bound to different DNA motifs were successively solved by X-ray crystallogra...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500705j
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::The Common Instrument Middleware Architecture (CIMA) aims at Grid-enabling a wide range of scientific instruments and sensors to enable easy access to and sharing and storage of data produced by these instruments and sensors. This paper describes the implementation of CIMA applied to the field of single-crystal X-ray ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci050368l
更新日期:2006-05-01 00:00:00
abstract::TAMkin is a program for the calculation and analysis of normal modes, thermochemical properties and chemical reaction rates. At present, the output from the frequently applied software programs ADF, CHARMM, CPMD, CP2K, Gaussian, Q-Chem, and VASP can be analyzed. The normal-mode analysis can be performed using a broad ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100099g
更新日期:2010-09-27 00:00:00