Abstract:
:Little attention has been given to the selection of trial descriptor sets when designing a QSAR analysis even though a great number of descriptor classes, and often a greater number of descriptors within a given class, are now available. This paper reports an effort to explore interrelationships between QSAR models and descriptor sets. Zhou and co-workers (Zhou et al., Nano Lett. 2008, 8 (3), 859-865) designed, synthesized, and tested a combinatorial library of 80 surface modified, that is decorated, multi-walled carbon nanotubes for their composite nanotoxicity using six endpoints all based on a common 0 to 100 activity scale. Each of the six endpoints for the 29 most nanotoxic decorated nanotubes were incorporated as the training set for this study. The study reported here includes trial descriptor sets for all possible combinations of MOE, VolSurf, and 4D-fingerprints (FP) descriptor classes, as well as including and excluding explicit spatial contributions from the nanotube. Optimized QSAR models were constructed from these multiple trial descriptor sets. It was found that (a) both the form and quality of the best QSAR models for each of the endpoints are distinct and (b) some endpoints are quite dependent upon 4D-FP descriptors of the entire nanotube-decorator complex. However, other endpoints yielded equally good models only using decorator descriptors with and without the decorator-only 4D-FP descriptors. Lastly, and most importantly, the quality, significance, and interpretation of a QSAR model were found to be critically dependent on the trial descriptor sets used within a given QSAR endpoint study.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Shao CY,Chen SZ,Su BH,Tseng YJ,Esposito EX,Hopfinger AJdoi
10.1021/ci3005308subject
Has Abstractpub_date
2013-01-28 00:00:00pages
142-58issue
1eissn
1549-9596issn
1549-960Xjournal_volume
53pub_type
杂志文章abstract::The efficiency of automated compound screening is heavily influenced by the design and the quality of the screening libraries used. We recently reported on the assembly of one diverse and one target-focused lead-like screening library. Using data from 15 enzyme-based screenings conducted using these libraries, their p...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300382f
更新日期:2013-03-25 00:00:00
abstract::In this paper, we introduce the BiKi Life Sciences suite. This software makes it easy for computational medicinal chemists to run ad hoc molecular dynamics protocols in a novel and task-oriented environment; as a notebook, BiKi (acronym of Binding Kinetics) keeps memory of any activity together with dependencies among...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00680
更新日期:2018-02-26 00:00:00
abstract::A homology model of the Arabidopsis thaliana UV resistance locus 8 (UVR8) protein is presented herein, showing a seven-bladed β-propeller conformation similar to the globular structure of RCC1. The UVR8 amino acid sequence contains a very high amount of conserved tryptophans, and the homology model shows that seven of...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200017f
更新日期:2011-06-27 00:00:00
abstract::A new methodology to describe the interactions in "receptor-ligand" complexes is presented. The methodology is based on a combination of the 3D/4D QSAR BiS/MC and CoCon algorithms. The first algorithm performs the restricted docking of compounds to receptor pockets. The second determines the relationships between the ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800405n
更新日期:2009-06-01 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::Cathepsin A is a mammalian lysosomal enzyme that catalyzes the hydrolysis of the carboxy-terminal amino acids of polypeptides and also regulates beta-galactosidase and neuraminidase-1 activities through the formation of a multienzymic complex in lysosomes. Human cathepsin A (hCathA), yeast carboxypeptidase (CPY), and ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci060093p
更新日期:2006-09-01 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::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::Peptide libraries allow researchers to quickly find hundreds of peptide sequences with a desired property. Currently, the large amount of data generated from peptide libraries is analyzed by hand, where researchers search for repeating patterns in the peptide sequences. Such patterns are called motifs. In this work, w...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300484q
更新日期:2013-02-25 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::In this account, a rapid retrosynthesis-based scoring method for the assessment of synthetic accessibility of drug-like molecules, called RASA (Retrosynthesis-based Assessment of Synthetic Accessibility) is devised. RASA first constructs a synthesis tree for the target molecule based on retrosynthetic analysis; in thi...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100216g
更新日期:2011-10-24 00:00:00
abstract::G protein-coupled receptors (GPCRs) represent the largest family of cell-surface receptors and about one-third of the actual targets of clinically used drugs. Following the progress made in the field of GPCRs structural determination, docking-based screening for novel potent and selective ligands is becoming an increa...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400532b
更新日期:2014-01-27 00:00:00
abstract::In this study, two probabilistic machine-learning algorithms were compared for in silico target prediction of bioactive molecules, namely the well-established Laplacian-modified Naïve Bayes classifier (NB) and the more recently introduced (to Cheminformatics) Parzen-Rosenblatt Window. Both classifiers were trained in ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300435j
更新日期:2013-08-26 00:00:00
abstract::Virtual screening is a powerful methodology to search for new small molecule inhibitors against a desired molecular target. Usually, it involves evaluating thousands of compounds (derived from large databases) in order to select a set of potential binders that will be tested in the wet-lab. The number of tested compou...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00241
更新日期:2017-08-28 00:00:00
abstract::Reversible covalent inhibitors have drawn increasing attention in drug design, as they are likely more potent than noncovalent inhibitors and less toxic than covalent inhibitors. Despite those advantages, the computational prediction of reversible covalent binding presents a formidable challenge because the binding pr...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00959
更新日期:2019-05-28 00:00:00
abstract::Congeners are molecules based on the same carbon skeleton but are different by the number of substituents and/or a substitution pattern. Examples are 1-chloronaphthalene, 1,4-dichloronaphthalene, and 1,3,8-trichloronaphthalene. Various persistent organic pollutants (POPs) exist in the environment as families of congen...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300289b
更新日期:2012-11-26 00:00:00
abstract::We propose an improved solvent contact model to estimate the solvation free energy of an organic molecule from individual atomic contributions. The modification of the solvation model involves the optimization of three kinds of parameters in the solvation free energy function: atomic fragmental volume, maximum atomic ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci600453b
更新日期:2007-03-01 00:00:00
abstract::Sixteen FDA-approved drugs were investigated to elucidate their mechanisms of action (MOAs) and clinical functions by pathway analysis based on retrieved drug targets interacting with or affected by the investigated drugs. Protein and gene targets and associated pathways were obtained by data-mining of public database...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci4005354
更新日期:2014-02-24 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::The proton conduction of transmembrane influenza virus B M2 (BM2) proton channel is possibly mediated by the membrane environment, but the detailed molecular mechanism is challenging to determine. In this work, how membrane lipid composition regulates the conformation and hydration of BM2 channel is elucidated in sili...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00329
更新日期:2020-07-27 00:00:00
abstract::One tactic for cysteine protease inhibition is to form a covalent bond between an electrophilic atom of the inhibitor and the thiol of the catalytic cysteine. In this study, we evaluate the reaction free energy obtained from a hybrid quantum mechanical/molecular mechanical (QM/MM) free energy profile as a predictor of...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00847
更新日期:2020-02-24 00:00:00
abstract::SMIfp (SMILES fingerprint) is defined here as a scalar fingerprint describing organic molecules by counting the occurrences of 34 different symbols in their SMILES strings, which creates a 34-dimensional chemical space. Ligand-based virtual screening using the city-block distance CBD(SMIfp) as similarity measure provi...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci400206h
更新日期:2013-08-26 00:00:00
abstract::Small-molecule protein docking is an essential tool in drug design and to understand molecular recognition. In the present work we introduce FlexAID, a small-molecule docking algorithm that accounts for target side-chain flexibility and utilizes a soft scoring function, i.e. one that is not highly dependent on specifi...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00078
更新日期:2015-07-27 00:00:00
abstract::The quantitative structure-activity relationship (QSAR) approach has been used to model a wide range of chemical-induced biological responses. However, it had not been utilized to model chemical-induced genomewide gene expression changes until very recently, owing to the complexity of training and evaluating a very la...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00281
更新日期:2017-09-25 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::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::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::Development of accurate force field parameters for molecular ions in the context of a polarizable energy function based on the classical Drude oscillator is a crucial step toward an accurate polarizable model for modeling and simulations of biological macromolecules. Toward this goal we have undertaken a hierarchical ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00132
更新日期:2018-05-29 00:00:00
abstract::Grass weed populations resistant to acetyl-CoA carboxylase-inhibiting (ACCase; EC 6.4.1.2) herbicides represent a major problem for the sustainable development of modern agriculture. In the present study, extensive computational simulations, including homology modeling, molecular dynamics (MD) simulations, and molecul...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci900174d
更新日期:2009-08-01 00:00:00
abstract::We report here on long-time all-atomistic molecular dynamics simulations of functional supramolecular nanotubes composed by the self-assembly of peptide-drug amphiphiles (DAs). These DAs have been shown to possess an inherently high drug loading of the hydrophobic anticancer drug camptothecin. We probe the self-assemb...
journal_title:Journal of chemical information and modeling
pub_type: 信件
doi:10.1021/acs.jcim.8b00193
更新日期:2018-06-25 00:00:00