Abstract:
:The ligand binding determinants for the angiotensin II type 1 receptor (AT1R), a G protein-coupled receptor (GPCR), have been characterized by means of computer simulations. As a first step, a pharmacophore model of various known AT1R ligands exhibiting a wide range of binding affinities was generated. Second, a structural model of AT1R was built making use of the growing set of crystal structures of GPCRs, which was further used for the docking of the AT1R ligands based on the devised pharmacophore model. Next, ligand-receptor-lipid bilayer systems were studied by means of molecular dynamics (MD) simulations. Overall, the present study has permitted, combining the pharmacophore model with binding free energy calculations obtained from the MD simulations, to propose the molecular mechanisms by which sartans interact with AT1R.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Matsoukas MT,Cordomí A,Ríos S,Pardo L,Tselios Tdoi
10.1021/ci400400msubject
Has Abstractpub_date
2013-11-25 00:00:00pages
2874-83issue
11eissn
1549-9596issn
1549-960Xjournal_volume
53pub_type
杂志文章abstract::We describe a general methodology for designing an empirical scoring function and provide smina, a version of AutoDock Vina specially optimized to support high-throughput scoring and user-specified custom scoring functions. Using our general method, the unique capabilities of smina, a set of default interaction terms ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300604z
更新日期:2013-08-26 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::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 this work, the perception of similarity of reactions catalyzed by hydrolases and oxidoreductases on the basis of the overall breaking and making of bonds of reactions is investigated. Six physicochemical properties for the reacting bond in the substrate of each enzymatic reaction were calculated to describe the cha...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci9004833
更新日期:2010-06-28 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::We describe here our tool named PyPLIF HIPPOS, which was newly developed to analyze the docking results of AutoDock Vina and PLANTS. Its predecessor, PyPLIF (https://github.com/radifar/pyplif), is a molecular interaction fingerprinting tool for the docking results of PLANTS, exclusively. Unlike its predecessor, PyPLIF...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00305
更新日期:2020-08-24 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::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
更新日期:2007-09-01 00:00:00
abstract::Databases of small, potentially bioactive molecules are ubiquitous across the industry and academia. Designed such that each unique compound should appear only once, the multiplicity of ways in which many compounds can be represented means that these databases require methods for standardizing the representation of ch...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00232
更新日期:2020-08-24 00:00:00
abstract::Human type II topoisomerases, molecular motors that alter the DNA topology, are a major target of modern chemotherapy. Groups of catalytic inhibitors represent a new approach to overcome the known limitations of topoisomerase II poisons such as cardiotoxicity and induction of secondary tumors. Here, we present a class...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00202
更新日期:2020-07-27 00:00:00
abstract::In the present contribution, we have developed a database, called the FAR-database, where the acronym FAR stands for Fused Aromatic Rings, which presents the results of nuclear independent chemical shifts calculations, NICS(0), NICS(1), NICS(0)ZZ, and NICS(1)ZZ, of 660 neutral benzenoid-PAHs and cyclopenta-fused PAHs....
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00909
更新日期:2020-02-24 00:00:00
abstract::The community structure-activity resource (CSAR) data sets are used to develop and test a support vector machine-based scoring function in regression mode (SVR). Two scoring functions (SVR-KB and SVR-EP) are derived with the objective of reproducing the trend of the experimental binding affinities provided within the ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200078f
更新日期:2011-09-26 00:00:00
abstract::In the present work, the Henderson-Hasselbalch (HH) equation has been employed for the development of a tool for the prediction of pH-dependent aqueous solubility of drugs and drug candidates. A new prediction method for the intrinsic solubility was developed, based on artificial neural networks that have been trained...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600292q
更新日期:2006-11-01 00:00:00
abstract::Structure-based virtual screening is highly used in the early stages of drug discovery to identify new putative lead compounds for a given target. However, when a small molecule elicits a biological effect, but its target is unknown, or the side effects it causes arise from its undesired interaction with unknown count...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00428
更新日期:2019-11-25 00:00:00
abstract::In the present study, we report the exploration of binding modes of potent HIV-1 integrase (IN) inhibitors MK-0518 (raltegravir) and GS-9137 (elvitegravir) as well as chalcone and related amide IN inhibitors we recently synthesized and the development of 3D-QSAR models for integrase inhibition. Homology models of DNA-...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200485a
更新日期:2012-02-27 00:00:00
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 orbit...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800001m
更新日期:2008-05-01 00:00:00
abstract::The cannabinoid receptor subtype 2 (CB2) is a promising therapeutic target for blood cancer, pain relief, osteoporosis, and immune system disease. The recent withdrawal of Rimonabant, which targets another closely related cannabinoid receptor (CB1), accentuates the importance of selectivity for the development of CB2 ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci3003914
更新日期:2013-01-28 00:00:00
abstract::Modern industrial lubricants are often blended with an assortment of chemical additives to improve the performance of the base stock. Machine learning-based predictive models allow fast and veracious derivation of material properties and facilitate novel and innovative material designs. In this study, we outline the d...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b01068
更新日期:2020-03-23 00:00:00
abstract::Ab initio quantum-chemistry programs produce and use large amounts of data, which are usually stored on disk in the form of binary files. A FORTRAN library, named Q5Cost, has been designed and implemented in order to allow the storage of these data sets in a special data format built with the HDF5 technology. This dat...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci7000567
更新日期:2007-05-01 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::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
abstract::We report a new classification method for pyranose ring conformations called Best-fit, Four-Membered Plane (BFMP), which describes pyranose ring conformations based on reference planes defined by four atoms. The method is able to characterize all asymmetrical and symmetrical shapes of a pyran ring, is readily automate...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500325b
更新日期:2014-10-27 00:00:00
abstract::Traditionally, a drug potency is expressed in terms of thermodynamic quantities, mostly Kd, and empirical IC50 values. Although binding affinity as an estimate of drug activity remains relevant, it is increasingly clear that it is also important to include (un)binding kinetic parameters in the characterization of pote...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00518
更新日期:2018-11-26 00:00:00
abstract::The appropriate selection of a chemical space represented by the data set, the selection of its chemical data representation, the development of a correct modeling process using a robust and reproducible algorithm, and the performance of an exhaustive training and external validation determine the usability and reprod...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00492
更新日期:2017-11-27 00:00:00
abstract::Protein dynamics play a critical role in ligand binding, and different models have been proposed to explain the relationships between protein motion and molecular recognition. Here, we present a study of ligand-binding processes associated with large conformational changes of a protein to elucidate the critical choice...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00125
更新日期:2017-07-24 00:00:00
abstract::This paper presents an exploratory study of a novel method for flexible 3-D similarity searching based on autocorrelation vectors and smoothed bounded distance matrices. Although the new approach is unable to outperform an existing 2-D similarity searching in terms of enrichment factors, it is able to retrieve differe...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci0503863
更新日期:2006-03-01 00:00:00
abstract::A database has been derived from recently reported [60]fullerene derivatives, and their binding scores with HIV-1 PR have been computed using docking techniques. Computational methods have been used to predict which derivatives may have high binding affinities, and for these compounds biological tests have been perfor...
journal_title:Journal of chemical information and modeling
pub_type: 信件
doi:10.1021/ci900047s
更新日期:2009-05-01 00:00:00
abstract::In structure-based drug design, scoring functions are often employed to evaluate protein-ligand interactions. A variety of scoring functions have been developed so far, and thus, some objective benchmarks are desired for assessing their strength and weakness. The comparative assessment of scoring functions (CASF) benc...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00545
更新日期:2019-02-25 00:00:00
abstract::A new variable selection wrapper method named the Monte Carlo variable selection (MCVS) method was developed utilizing the framework of the Monte Carlo cross-validation (MCCV) approach. The MCVS method reports the variable selection results in the most conventional and common measure of statistical hypothesis testing,...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700283s
更新日期:2008-02-01 00:00:00
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
更新日期:2014-03-24 00:00:00