Abstract：
:We develop the idea that the use of ad hoc molecular descriptors in QSAR/QSPR studies is not an optimal solution. Instead, we propose to optimize these descriptors for the specific properties under study. In the case of topological indices (TIs) we propose the use of the generalized topological indices (GTIs), which account for several of the classical TIs in one single graph invariant. GTIs represent points in a six-dimensional space of topological parameters, which can be optimized for describing a specific property. The situation shows some resemblance with the geometry optimization procedures used to minimize molecular energy. Here we study the reaction rate coefficients for the gas-phase radical reactions between alkanes and cycloalkanes with OH, Cl, and NO3 radicals. These reaction rate coefficients were studied recently by using some "classical" TIs, such as Balaban and Randić indices. Despite the fact that the Randić index produces acceptable QSPR models for some of these reactions, the models developed are still far from being optimal. Using the GTI approach we have improved these QSPRs by reducing the standard deviation by almost 50%. In addition, the current approach permits the illustration of the similarities and differences among the different descriptors studied, indicating possible directions for searching new optimal molecular descriptors.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Estrada E,Matamala ARdoi
10.1021/ci600448bsubject
Has Abstractpub_date
2007-05-01 00:00:00pages
794-804issue
3eissn
1549-9596issn
1549-960Xjournal_volume
47pub_type
杂志文章abstract：:Artificial intelligence and multiobjective optimization represent promising solutions to bridge chemical and biological landscapes by addressing the automated de novo design of compounds as a result of a humanlike creative process. In the present study, we conceived a novel pair-based multiobjective approach implement...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00517
更新日期：2020-10-26 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：:Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern. Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y NA. However, most of the reported studies on H2...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00331
更新日期：2016-01-25 00:00:00
abstract：:The concept of chemoisosterism of protein environments is introduced as the complementary property to bioisosterism of chemical fragments. In the same way that two chemical fragments are considered bioisosteric if they can bind to the same protein environment, two protein environments will be considered chemoisosteric...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci3002974
更新日期：2013-02-25 00:00:00
abstract：:In this work, we report an ab initio investigation based on density functional theory calculations within van der Waals D3 corrections to investigate the adsorption properties and activation of CO2 on transition-metal (TM) 13-atom clusters (TM = Ru, Rh, Pd, Ag), which is a key step for the development of subnano catal...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00792
更新日期：2020-02-24 00:00:00
abstract：:Target-oriented substructure-based virtual screening (sSBVS) of molecules is a promising approach in drug discovery. Yet, there are doubts whether sSBVS is suitable also for extrapolation, that is, for detecting molecules that are very different from those used for training. Herein, we evaluate the predictive power of...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200472s
更新日期：2012-03-26 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
abstract：:The Torsion Library contains hundreds of rules for small molecule conformations which have been derived from the Cambridge Structural Database (CSD) and are curated by molecular design experts. The torsion rules are encoded as SMARTS patterns and categorize rotatable bonds via a traffic light coloring scheme. We have ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00522
更新日期：2016-01-25 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：:The reuptake of neurotransmitters by dopamine, norepinephrine, and serotonin transporters during neuronal transmission requires a sodium gradient. An "ionic mode" of binding proposes that aspartate anchors the ligand's positive charge but ignores the direct role of sodium in ligand binding seen in the only representat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700255d
更新日期：2008-07-01 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：:Peptides that bind to ion channels have attracted much interest as potential lead molecules for the development of new drugs and insecticides. However, the structure determination of large peptide-channel complexes using experimental methods is challenging. Thus structural models are often derived from combining exper...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00529
更新日期：2016-01-25 00:00:00
abstract：:The partitioning of amino acids between water and apolar environments is of vital importance in protein function and drug delivery. Here we present an extensive benchmark for octanol/water (log Poct), chloroform/water (log Pclf), and cyclohexane/water (log Pchx) partition coefficients of neutral amino acid side chain ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00493
更新日期：2018-08-27 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：:The large volume of protein-ligand structures now available enables innovative and efficient protocols in computational FBDD (Fragment-Based Drug Design) to be proposed based on experimental data. In this work, we build a database of MED-Portions, where a MED-Portion is a new structural object encoding protein-fragmen...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci8003094
更新日期：2009-02-01 00:00:00
abstract：:In this study, we used the Martini Coarse-Grained model with no applied restraints to predict the binding mode of some peptides to G-Protein Coupled Receptors (GPCRs). Both the Neurotensin-1 and the chemokine CXCR4 receptors were used as test cases. Their ligands, NTS8-13 and CVX15 peptides, respectively, were initial...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00503
更新日期：2017-03-27 00:00:00
abstract：:Atomic neural networks (ANNs) constitute a class of machine learning methods for predicting potential energy surfaces and physicochemical properties of molecules and materials. Despite many successes, developing interpretable ANN architectures and implementing existing ones efficiently are still challenging. This call...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00994
更新日期：2020-03-23 00:00:00
abstract：:The yeast protein GCN4 is a transcriptional activator in the basic leucine zipper (bZip) family, whose distinguishing feature is the "chopstick-like" homodimer of alpha helices formed at the DNA-binding interface. While experiments have shown that truncated versions of the protein retain biologically relevant DNA-bind...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500448e
更新日期：2014-10-27 00:00:00
abstract：:The recent article "Evaluation of pK(a) Estimation Methods on 211 Druglike Compounds" ( Manchester, J.; et al. J. Chem Inf. Model. 2010, 50, 565-571 ) reports poor results for the program Epik. Here, we highlight likely sources for the poor performance and describe work done to improve the performance. Running Epik in...
journal_title：Journal of chemical information and modeling
pub_type： 评论,杂志文章
doi：10.1021/ci100332m
更新日期：2011-01-24 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：:Fragment complementation is gaining an increasing impact as a nonperturbing method to probe noncovalent interactions within protein supersecondary structures. In this study, the fast Fourier transform rigid-body docking algorithm ZDOCK has been employed for in silico reconstitution of the calcium binding protein calbi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0501995
更新日期：2005-09-01 00:00:00
abstract：:Estrogens exert important physiological effects through the modulation of two human estrogen receptor (hER) subtypes, alpha (hERalpha) and beta (hERbeta). Because the levels and relative proportion of hERalpha and hERbeta differ significantly in different target cells, selective hER ligands could target specific tissu...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci8002182
更新日期：2008-11-01 00:00:00
abstract：:Pharmacophore hypotheses were developed for six structurally diverse series of cholecystokinin-B/gastrin receptor (CCK-BR) antagonists. A training set consisting of 33 compounds was carefully selected. The activity spread of the training set molecules was from 0.1 to 2100 nM. The most predictive pharmacophore model (h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050257m
更新日期：2005-11-01 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：:3-Phosphoinositide-dependent protein kinase-1 (PDK1) is a promising target for developing novel anticancer drugs. In order to understand the structure-activity correlation of indolinone-based PDK1 inhibitors, we have carried out a combined molecular docking and three-dimensional quantitative structure-activity relatio...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800147v
更新日期：2008-09-01 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：:Membrane fusion, a key step in the early stages of virus propagation, allows the release of the viral genome in the host cell cytoplasm. The process is initiated by fusion peptides that are small, hydrophobic components of viral membrane-embedded glycoproteins and are typically conserved within virus families. Here, w...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c01231
更新日期：2021-01-25 00:00:00
abstract：:Halogen bonds (XBs) are attracting increasing attention in biological systems. Protein Data Bank (PDB) archives experimentally determined XBs in biological macromolecules. However, no software for structure refinement in X-ray crystallography takes into account XBs, which might result in the weakening or even vanishin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00235
更新日期：2017-07-24 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：: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
