Abstract：
:We propose a hypothesis that "a model of active compound can be provided by integrating information of compounds high-ranked by docking simulation of a random compound library". In our hypothesis, the inclusion of true active compounds in the high-ranked compound is not necessary. We regard the high-ranked compounds as being pseudo-active compounds. As a method to embody our hypothesis, we introduce a pseudo-structure-activity relationship (PSAR) model. Although the PSAR model is the same as a quantitative structure activity relationship (QSAR) model, in terms of statistical methodology, the implications of the training data are different. Known active compounds (ligands) are used as training data in the QSAR model, whereas the pseudo-active compounds are used in the PSAR model. In this study, Random Forest was used as a machine-learning algorithm. From tests for four functionally different targets, estrogen receptor antagonist (ER), thymidine kinase (TK), thrombin, and acetylcholine esterase (AChE), using five scoring functions, we obtained three conclusions: (1) the PSAR models significantly gave higher percentages of known ligands found than random sampling, and these results are sufficient to support our hypothesis; (2) the PSAR models gave higher percentages of known ligands found than normal scoring by scoring function, and these results demonstrate the practical usefulness of the PSAR model; and (3) the PSAR model can assess compounds failed in the docking simulation. Note that PSAR and QSAR models are used in different situations; the advantage of the PSAR model emerges when no ligand is available as training data or when one wants to find novel types of ligands, whereas the QSAR model is effective for finding compounds similar to known ligands when the ligands are already known.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Fukunishi H,Teramoto R,Shimada Jdoi
10.1021/ci7003384subject
Has Abstractpub_date
2008-03-01 00:00:00pages
575-82issue
3eissn
1549-9596issn
1549-960Xjournal_volume
48pub_type
杂志文章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：:Here, a method is described for easily building three-carbon nanotube junctions. It allows the geometry to be found and bond connectivity of C(3) symmetric nanotube junctions to be established. Such junctions may present a variable degree of pyramidalization and are composed of three identical carbon nanotubes with ar...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200056p
更新日期：2011-06-27 00:00:00
abstract：:The sensitivity of docking calculations to the geometry of the input ligand was studied. It was found that even small changes in the ligand input conformation can lead to large differences in the geometries and scores of the resulting docked poses. The accuracy of docked poses produced from different ligand input stru...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9000629
更新日期：2009-07-01 00:00:00
abstract：:We have applied the two most commonly used methods for automatic matched pair identification, obtained the optimum settings, and discovered that the two methods are synergistic. A turbocharging approach to matched pair analysis is advocated in which a first round (a conservative categorical approach that uses an analo...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00335
更新日期：2017-10-23 00:00:00
abstract：:An essential feature of all practical de novo molecule generating programs is the ability to focus the potential combinatorial explosion of grown molecules on a desired chemical space. It is a daunting task to balance the generation of new molecules with limitations on growth that produce desired features such as stab...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9000458
更新日期：2009-07-01 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：:Template CoMFA, a novel alignment methodology for training or test set structures in 3D-QSAR, is introduced. Its two most significant advantages are its complete automation and its ability to derive a single combined model from multiple structural series affecting a biological target. Its only two inputs are one or mo...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400696v
更新日期：2014-02-24 00:00:00
abstract：:Advances in computer-aided translation technology have made tremendous progress in accuracy in the past few years. Chemical Abstracts Service of the American Chemical Society summarizes scientific works from more than 50 languages and allows the users to search papers in nine selected languages. Currently, only the ab...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00274
更新日期：2020-07-27 00:00:00
abstract：:In this article, we present a systematic way to classify a family of high-genus fullerenes (HGFs) by decomposing them into two types of necklike structures, which are the negatively curved parts of parent toroidal carbon nanotubes. By replacing the faces of a uniform polyhedron with these necks, an HGF polyhedron corr...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9001124
更新日期：2009-07-01 00:00:00
abstract：:Following the theoretical model by Hann et al. moderately complex structures are preferable lead compounds since they lead to specific binding events involving the complete ligand molecule. To make this concept usable in practice for library design, we studied several complexity measures on the biological activity of ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0503558
更新日期：2006-03-01 00:00:00
abstract：:Small molecule flexible alignment is a critical component of both ligand- and structure-based methods in computer-aided drug discovery. Despite its importance, the availability of high-quality flexible alignment software packages is limited. Here, we present BCL::MolAlign, a freely available property-based molecular a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00020
更新日期：2019-02-25 00:00:00
abstract：:The molecular structure of four dimeric units (D-E, E-F, F-G, and G-H) of the DEFGH structural unit of heparin, their anionic forms, and their sodium salts have been studied using the B3LYP/6-31+G(d) method. The optimized geometries indicate that the most stable structure of these dimeric units in neutral state is sta...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci060060+
更新日期：2006-07-01 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 investigate unexpectedly short non-covalent distances (<85% of the sum of van der Waals radii) in X-ray crystal structures of proteins. We curate over 11 000 high-quality protein crystal structures and an ultra-high-resolution (1.2 Å or better) subset containing >900 structures. Although our non-covalent distance c...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00144
更新日期：2019-05-28 00:00:00
abstract：:The goal of the present study was to ascertain the differential performance of a long molecular dynamics trajectory versus several shorter ones starting from different points in the phase space and covering the same sampling time. For this purpose, we selected the 16-mer peptide Bak16BH3 as a model for study and carri...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00347
更新日期：2016-10-24 00:00:00
abstract：:Discovery of new antibacterial agents is a never-ending task of medicinal chemistry. Every new drug brings significant improvement to patients with bacterial infections, but prolonged usage of antibacterials leads to the emergence of resistant strains. Therefore, novel active structures with new modes of action are re...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00436
更新日期：2019-11-25 00:00:00
abstract：:Molecular docking programs are widely used modeling tools for predicting ligand binding modes and structure based virtual screening. In this study, six molecular docking programs (DOCK, FlexX, GLIDE, ICM, PhDOCK, and Surflex) were evaluated using metrics intended to assess docking pose and virtual screening accuracy. ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900056c
更新日期：2009-06-01 00:00:00
abstract：:A new structure classification scheme for biopolymers is introduced, which is solely based on main-chain dihedral angles. It is shown that by dividing a biopolymer into segments containing two central residues, a local classification can be performed. The method is referred to as DISICL, short for Dihedral-based Segme...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400541d
更新日期：2014-01-27 00:00:00
abstract：:The study of chromatographic retention of natural products can be used to increase their identification speed in complex biological matrices. In this work, six variables were used to study the retention behavior in reversed phase liquid chromatography of 39 sesquiterpene lactones (SL) from an in-house database using c...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500581q
更新日期：2015-01-26 00:00:00
abstract：:Encapsulation of peptide and protein-based drugs in polymeric nanoparticles is one of the fundamental fields in controlled-release drug delivery systems. The molecular mechanisms of absorption of peptides to the polymeric nanoparticles are still unknown, and there is no precise molecular data on the encapsulation proc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00641
更新日期：2019-01-28 00:00:00
abstract：:Extending the original training data with simulated unobserved data points has proven powerful to increase both the generalization ability of predictive models and their robustness against changes in the structure of data (e.g., systematic drifts in the response variable) in diverse areas such as the analysis of spect...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00570
更新日期：2015-12-28 00:00:00
abstract：:Simulating protein flexibility is a major issue in the docking-based drug-design process for which a single methodological solution does not exist. In our search of new anti-Alzheimer ligands, we were faced with the challenge of including receptor plasticity in a virtual screening campaign aimed at finding new β-secre...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300390h
更新日期：2012-10-22 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：: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：:An index of the activation of Class A G-protein-coupled receptors (GPCRs) has been trained using interhelix distances from a series of microsecond molecular-dynamics simulations and tested for 268 published X-ray structures. In a three-class model that includes intermediate structures, 63% of the active structures are...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00604
更新日期：2019-09-23 00:00:00
abstract：:Standardization is used to ensure that the variables in a similarity calculation make an equal contribution to the computed similarity value. This paper compares the use of seven different methods that have been suggested previously for the standardization of integer-valued or real-valued data, comparing the results w...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800224h
更新日期：2009-02-01 00:00:00
abstract：:Membrane-bound protein receptors are a primary biological drug target, but the computational analysis of membrane proteins has been limited. In order to improve molecular mechanics Poisson-Boltzmann surface area (MMPBSA) binding free energy calculations for membrane protein-ligand systems, we have optimized a new hete...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00363
更新日期：2019-06-24 00:00:00
abstract：:Chemical structure extraction from documents remains a hard problem because of both false positive identification of structures during segmentation and errors in the predicted structures. Current approaches rely on handcrafted rules and subroutines that perform reasonably well generally but still routinely encounter s...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00669
更新日期：2019-03-25 00:00:00
abstract：:Moving to a new country, with a different culture and a new environment, is not an easy decision. In this perspective, I present some reasons that made me, a Brazilian computational biochemist, move abroad to do postdoctoral research and some of the challenges I faced before and after moving. ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00764
更新日期：2020-02-24 00:00:00
abstract：:The spatial sign is a multivariate extension of the concept of sign. Recently multivariate estimators of covariance structures based on spatial signs have been examined by various authors. These new estimators are found to be robust to outlying observations. From a computational point of view, estimators based on spat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050498u
更新日期：2006-05-01 00:00:00
