Abstract：
:A data set of 130 diverse compounds containing both central nervous system (CNS) and non-CNS drugs was used to generate a renal clearance model using a classical Volsurf approach. Percentage renal clearance data was used as a biological input. The score plots obtained from principal component analysis and partial least-squares (PLS) analysis clearly separated high-clearance compounds from low-clearance compounds. PLS models were used to predict the renal clearance of the data set. Categorical statistical methods such as SIMCA and recursive partitioning techniques were used for classifying the compounds into low- and high-clearance categories. PLS coefficient plots, Volsurf descriptor profiles, 3D Grid maps, and RP decision trees were used to explain the important descriptors separating low and high renal clearance compounds. For comparative purposes, topological descriptors such as Molconn-Z were also examined. All the models were validated by an external test set of 20 compounds. These models can be used as efficient tools in the classification and prediction of the renal clearance of unknown compounds, the knowledge of which is helpful in understanding their bioavailability behavior.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Doddareddy MR,Cho YS,Koh HY,Kim DH,Pae ANdoi
10.1021/ci0503309subject
Has Abstractpub_date
2006-05-01 00:00:00pages
1312-20issue
3eissn
1549-9596issn
1549-960Xjournal_volume
46pub_type
杂志文章abstract：:An ultrafast docking and virtual screening program, CRDOCK, is presented that contains (1) a search engine that can use a variety of sampling methods and an initial energy evaluation function, (2) several energy minimization algorithms for fine tuning the binding poses, and (3) different scoring functions. This modula...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300194a
更新日期：2012-08-27 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：:The hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase (RdRP) is a crucial and unique component of the HCV RNA replication machinery and a validated target for drug discovery. Multiple crystal structures of NS5B inhibitor complexes have facilitated the identification of novel compound scaffolds through in silic...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400644r
更新日期：2014-02-24 00:00:00
abstract：:Generalization of an earlier algorithm has led to the development of new local structural alignment algorithms for prediction of protein-protein binding sites. The algorithms use maximum cliques on protein graphs to define structurally similar protein regions. The search for structural neighbors in the new algorithms ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100265x
更新日期：2010-10-25 00:00:00
abstract：:Methods that rapidly evaluate molecular complexity and synthetic feasibility are becoming increasingly important for in silico chemistry. We propose a new metric based on relative atomic electronegativities and bond parameters that evaluate both synthetic and molecular complexity (SMCM) starting from chemical structur...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0501387
更新日期：2005-09-01 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：:Computer programs for structure diagram generation (SDG) are indispensable cheminformatic tools that translate one- or three-dimensional (1D or 3D) chemical structure data stored in electronic formats to human-readable 2D depictions. Although many such programs are known, only a moderate part of chemical space can be ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00391
更新日期：2016-12-27 00:00:00
abstract：:The protection exerted by 3,5-dihydroxy-4-methoxybenzyl alcohol (DHMBA), a phenolic compound recently isolated from the Pacific oyster, against oxidative stress (OS) is investigated using the density functional theory. Our results indicate that DHMBA is an outstanding peroxyl radical scavenger, being about 15 times an...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00513
更新日期：2015-12-28 00:00:00
abstract：:Due to the importance of hot-spots (HS) detection and the efficiency of computational methodologies, several HS detecting approaches have been developed. The current paper presents new models to predict HS for protein-protein and protein-nucleic acid interactions with better statistics compared with the ones currently...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500760m
更新日期：2015-05-26 00:00:00
abstract：:This paper introduces the concept of an isomer network based on the reaction step counts between pairs of isomers as an alternative means to view and analyze isomer space. The computation of isomer networks is computationally expensive with respect to both run time and memory. Accordingly, this paper focuses on the de...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci4005173
更新日期：2014-01-27 00:00:00
abstract：:We present a theoretical study on the performance of ensemble docking methodologies considering multiple protein structures. We perform a theoretical analysis of pose prediction experiments which is completely unbiased, as we make no assumptions about specific scoring functions, search paradigms, protein structures, o...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci2002796
更新日期：2011-11-28 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：:A giant technological leap in the field of cryo-electron microscopy (cryo-EM) has assured the achievement of near-atomic resolution structures of biological macromolecules. As a recognition of this accomplishment, the Nobel Prize in Chemistry was awarded in 2017 to Jacques Dubochet, Joachim Frank, and Richard Henderso...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b01015
更新日期：2020-05-26 00:00:00
abstract：:Identifying drug-target interactions (DTIs) plays an important role in the field of drug discovery, drug side-effects, and drug repositioning. However, in vivo or biochemical experimental methods for identifying new DTIs are extremely expensive and time-consuming. Recently, in silico or various computational methods h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00408
更新日期：2019-07-22 00:00:00
abstract：:The dissolution of a chemical into water is a process fundamental to both chemistry and biology. The persistence of a chemical within the environment and the effects of a chemical within the body are dependent primarily upon aqueous solubility. With the well-documented limitations hindering the accurate experimental d...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900286s
更新日期：2009-11-01 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
abstract：:In this work, we present a systematical investigation of the influence of ligand protonation states, stereoisomers, and tautomers on results obtained with the two protein-ligand docking programs GOLD and PLANTS. These different states were generated with a fully automated tool, called SPORES (Structure PrOtonation and...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800420z
更新日期：2009-06-01 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：: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：:We have studied the binding affinities of a set of 45 small-molecule inhibitors to protein tyrosine phosphatase 1B (PTP1B) through computational approaches. All of these compounds share a common oxalylamino benzoic acid (OBA) moiety. The complex structure of each compound was modeled by using the GOLD program plus the...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci8004429
更新日期：2009-04-01 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：: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：:How well do different classification methods perform in selecting the ligands of a protein target out of large compound collections not used to train the model? Support vector machines, random forest, artificial neural networks, k-nearest-neighbor classification with genetic-algorithm-optimized feature selection, tren...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050519k
更新日期：2006-05-01 00:00:00
abstract：:The three-dimensional structures of 3-anilino-4-arylmaleimides, selective GSK-3beta inhibitors, were correlated to their biological affinities by 3D-QSAR studies (CoMFA method). The cocrystallographic data of GSK-3beta vs 3-anilino-4-arylmaleimide allowed us to compare 3D-QSAR results to experimental intermolecular in...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050008y
更新日期：2005-05-01 00:00:00
abstract：:Maltose-binding protein is a periplasmic binding protein responsible for transport of maltooligosaccarides through the periplasmic space of Gram-negative bacteria, as a part of the ABC transport system. The molecular mechanisms of the initial ligand binding and induced large scale motion of the protein's domains still...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500520q
更新日期：2015-02-23 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：: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：:Up to now, publicly available data sets to build and evaluate Ames mutagenicity prediction tools have been very limited in terms of size and chemical space covered. In this report we describe a new unique public Ames mutagenicity data set comprising about 6500 nonconfidential compounds (available as SMILES strings and...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900161g
更新日期：2009-09-01 00:00:00
abstract：:Nonfibrillar neurotoxic amyloid β (Aβ) oligomer structures are typically rich in β-sheets, which could be promoted by metal ions like Zn(2+). Here, using molecular dynamics (MD) simulations, we systematically examined combinations of Aβ40 peptide conformations and Zn(2+) binding modes to probe the effects of secondary...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00063
更新日期：2015-06-22 00:00:00
abstract：:We have performed a ligand coordinate analysis to monitor the movement of the inhibitor SC-558 from the active site of the COX-2 protein to the exterior using molecular dynamics techniques. This study provides an insight into the intermolecular interactions formed by the ligand during this journey. The published cryst...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050142i
更新日期：2006-07-01 00:00:00
