Abstract:
:The possibility of improving the predictive ability of comparative molecular field analysis (CoMFA) by settings optimization has been evaluated to show that CoMFA predictive ability can be improved. Ten different CoMFA settings are evaluated, producing a total of 6120 models. This method has been applied to nine different data sets, including the widely used benchmark steroid data set, as well as eight other data sets proposed as QSAR benchmarking data sets by Sutherland et al. (J. Med. Chem. 2004, 47, 5541-5554). All data sets have been studied using training and test sets to allow for both internal (q(2)) and external (r(2)(pred)) predictive ability assessment. CoMFA settings optimization was successful in developing models with improved q(2) and r(2)(pred) as compared to default CoMFA modeling. Optimized CoMFA is compared with comparative molecular similarity indices analysis (CoMSIA) and holographic quantitative structure-activity relationship (HQSAR) models and found to consistently produce models with improved or equivalent q(2) and r(2)(pred). The ability of settings optimization to improve model predictive ability has been validated using both internal and external predictions, and the risk of chance correlation has been evaluated using response variable randomization tests.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Peterson SD,Schaal W,Karlén Adoi
10.1021/ci049612jkeywords:
subject
Has Abstractpub_date
2006-01-01 00:00:00pages
355-64issue
1eissn
1549-9596issn
1549-960Xjournal_volume
46pub_type
杂志文章abstract::The human cytochrome P450 1A2 is an important drug metabolizing and procarcinogen activating enzyme. An experimental study found that a peripheral mutation, F186L, at ∼26 Å away from the enzyme's active site, caused a significant reduction in the enzymatic activity of 1A2 deethylation reactions. In this paper, we expl...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200112b
更新日期:2011-06-27 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::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::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::Distribution patterns of 8411 compounds from 240 Chinese herbs were analyzed in relation to the herbal categories of traditional Chinese medicine (TCM), using Random Forest (RF) and self-organizing maps (SOM). RF was used first to construct TCM profiles of individual compounds, which describe their affinities for 28 m...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700155t
更新日期:2007-11-01 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::Arachidonic acid is an essential fatty acid in cells, acting as a key inflammatory intermediate in inflammatory reactions. In cardiac tissues, CYP2J2 can adopt arachidonic acid as a major substrate to produce epoxyeicosatrienoic acids (EETs), which can protect endothelial cells from ischemic or hypoxic injuries and ha...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400003p
更新日期:2013-06-24 00:00:00
abstract::Traditional herbal medicine has been an inseparable part of the traditional medical science in many countries throughout history. Nowadays, the popularity of using herbal medicines in daily life, as well as clinical practices, has gradually expanded to numerous Western countries with positive impacts and acceptance. T...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00826
更新日期:2020-03-23 00:00:00
abstract::The antiproliferative factor (APF) involved in interstitial cystitis is a glycosylated nonapeptide (TVPAAVVVA) containing a sialylated core 1 α-O-disaccharide linked to the N-terminal threonine. The chemical structure of APF was deduced using spectroscopic techniques and confirmed using total synthesis. The synthetic ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400147s
更新日期:2013-05-24 00:00:00
abstract::Protein-protein interactions are central to many biological processes, from intracellular communication to cytoskeleton assembly, and therefore represent an important class of targets for new therapeutics. The most common secondary structure in natural proteins is an α-helix. Small molecules seem to be attractive cand...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200424a
更新日期:2012-02-27 00:00:00
abstract::Inhibition of protein-protein interactions (PPIs) is emerging as a promising therapeutic strategy despite the difficulty in targeting such interfaces with drug-like small molecules. PPIs generally feature large and flat binding surfaces as compared to typical drug targets. These features pose a challenge for structura...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00103
更新日期:2015-08-24 00:00:00
abstract::The prediction of Log P is usually accomplished using either substructure or whole-molecule approaches. However, these methods are complicated, and previous whole-molecule approaches have not been successful for the prediction of Log P in very complex molecules. The observed chemical shifts in nuclear magnetic resonan...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci049643e
更新日期:2005-03-01 00:00:00
abstract::This paper is an overview of the most significant and impactful interpretation approaches of quantitative structure-activity relationship (QSAR) models, their development, and application. The evolution of the interpretation paradigm from "model → descriptors → (structure)" to "model → structure" is indicated. The lat...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章,评审
doi:10.1021/acs.jcim.7b00274
更新日期:2017-11-27 00:00:00
abstract::Three-dimensional protein structures are a key requisite for structure-based drug discovery. For many highly relevant targets, medicinal chemists are confronted with large numbers of target structures in their apo-forms or in complex with a wealth of different ligands. To exploit the full potential of such structure e...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00051
更新日期:2020-04-27 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::The integration of ligand- and structure-based strategies might sensitively increase the success of drug discovery process. We have recently described the application of Molecular Electrostatic Potential autocorrelated vectors (autoMEPs) in generating both linear (Partial Least-Square, PLS) and nonlinear (Response Sur...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci700300w
更新日期:2008-02-01 00:00:00
abstract::Human telomeric DNA G-quadruplex has been identified as a good therapeutic target in cancer treatment. G-quadruplex-specific ligands that stabilize the G-quadruplex have great potential to be developed as anticancer agents. Two crystal structures (an apo form of parallel stranded human telomeric G-quadruplex and its h...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00287
更新日期:2017-11-27 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::Compounds with high-confidence target annotations and activity measurements in the original and current release of the ChEMBL database have been compared to better understand how the growth of compound activity data might influence the spectrum of ligand-target interactions and the degree of target promiscuity among a...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci3003304
更新日期:2012-10-22 00:00:00
abstract::We examine the sensitivity of folding molecular dynamics simulations on the choice between three variants of the same force field (the AMBER99SB force field and its ILDN, NMR-ILDN, and STAR-ILDN variants). Using two different peptide systems (a marginally stable helical peptide and a β-hairpin) and a grand total of mo...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00493
更新日期:2016-10-24 00:00:00
abstract::Group 1 metabotropic glutamate receptors (mGluR) are G-protein coupled receptors with a large bilobate extracellular ligand binding region (LBR) that resembles a Venus fly trap. Closing of this LBR in the presence of a ligand is associated with the activation of the receptor. From conformational sampling of the LBR-li...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400160x
更新日期:2013-06-24 00:00:00
abstract::Great attention has been paid to the clinical significance of phosphodiesterase 5 (PDE5) inhibitors, such as sildenafil, tadalafil, and vardenafil widely used for erectile dysfunction. However, sildenafil causes side effects on visual functions since it shows similar potencies to inhibit PDE5 and PDE6, whereas tadalaf...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400458z
更新日期:2013-11-25 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::Since many projects at pharmaceutical organizations get their start from a high-throughput screening (HTS) campaign, improving the quality of the HTS deck can improve the likelihood of discovering a high-quality lead molecule that can be progressed to a drug candidate. Over the past decade, Janssen has implemented sev...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00258
更新日期:2018-10-22 00:00:00
abstract::Herein we present the VMD Store, an open-source VMD plugin that simplifies the way that users browse, discover, install, update, and uninstall extensions for the Visual Molecular Dynamics (VMD) software. The VMD Store obtains data about all the indexed VMD extensions hosted on GitHub and presents a one-click mechanism...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00739
更新日期:2019-11-25 00:00:00
abstract::A major concern of chemogenomics is to associate drug activity with biological variables. Several reports have clustered cell line drug activity profiles as well as drug activity-gene expression correlation profiles and noted that the resulting groupings differ but still reflect mechanism of action. The present paper ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci060073n
更新日期:2007-01-01 00:00:00
abstract::The homodimeric catabolite activator protein (CAP) regulates the transcription of several bacterial genes based on the cellular concentration of cyclic adenosine monophosphate (cAMP). The binding of cAMP to CAP triggers allosteric communication between the cAMP binding domains (CBD) and DNA binding domains (DBD) of CA...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00617
更新日期:2020-12-28 00:00:00
abstract::Machine learning (ML) algorithms are gaining importance in the processing of chemical information and modeling of chemical reactivity problems. In this work, we have developed a perturbation-theory and machine learning (PTML) model combining perturbation theory (PT) and ML algorithms for predicting the yield of a give...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00286
更新日期:2018-07-23 00:00:00
abstract::Blockade of human ether-à-go-go related gene (hERG) channel prolongs the duration of the cardiac action potential and is a common reason for drug failure in preclinical safety trials. Therefore, it is of great importance to develop robust in silico tools to predict potential hERG blockers in the early stages of drug d...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200271d
更新日期:2011-11-28 00:00:00
abstract::Telomere maintenance is a universal cancer hallmark, and small molecules that disrupt telomere maintenance generally have anticancer properties. Since the vast majority of cancer cells utilize telomerase activity for telomere maintenance, the enzyme has been considered as an anticancer drug target. Recently, rational ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00336
更新日期:2015-12-28 00:00:00