Abstract：
:All molecules of up to 11 atoms of C, N, O, and F possible under consideration of simple valency, chemical stability, and synthetic feasibility rules were generated and collected in a database (GDB). GDB contains 26.4 million molecules (110.9 million stereoisomers), including three- and four-membered rings and triple bonds. By comparison, only 63 857 compounds of up to 11 atoms were found in public databases (a combination of PubChem, ChemACX, ChemSCX, NCI open database, and the Merck Index). A total of 538 of the 1208 ring systems in GDB are currently unknown in the CAS Registry and Beilstein databases in any carbon/heteroatom/multiple-bond combination or as a substructure. Over 70% of GDB molecules are chiral. Because of their small size, all compounds obey Lipinski's bioavailability rule. A total of 13.2 million compounds also follow Congreve's "Rule of 3" for lead-likeness. A Kohonen map trained with autocorrelation descriptors organizes GDB according to compound classes and shows that leadlike compounds are most abundant in chiral regions of fused carbocycles and fused heterocycles. The projection of known compounds into this map indicates large uncharted areas of chemical space. The potential of GDB for drug discovery is illustrated by virtual screening for kinase inhibitors, G-protein coupled receptor ligands, and ion-channel modulators. The database is available from the author's Web page.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Fink T,Reymond JLdoi
10.1021/ci600423usubject
Has Abstractpub_date
2007-03-01 00:00:00pages
342-53issue
2eissn
1549-9596issn
1549-960Xjournal_volume
47pub_type
杂志文章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：:As computational drug design becomes increasingly reliant on virtual screening and on high-throughput 3D modeling, the need for fast, robust, and reliable methods for sampling molecular conformations has become greater than ever. Furthermore, chemical novelty is at a premium, forcing medicinal chemists to explore more...
journal_title：Journal of chemical information and modeling
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doi：10.1021/ci900238a
更新日期：2009-10-01 00:00:00
abstract：:Solute-solvent interactions are critical for biomolecular stability and recognition. Explicit solvent molecular dynamics (MD) simulations are routinely used to probe such interactions. However, detailed analyses and interpretation of the hydration patterns seen in MD simulations can be both complex and time-consuming....
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00453
更新日期：2019-07-22 00:00:00
abstract：:Water is the natural medium of molecules in the cell and plays an important role in protein structure, function and interaction with small molecule ligands. However, the widely used molecular mechanics Poisson-Boltzmann surface area (MM/PBSA) method for binding energy calculation does not explicitly take account of wa...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci4001794
更新日期：2014-02-24 00:00:00
abstract：:Taking into account dynamical behavior and/or structural inaccuracies of receptor-ligand systems becomes increasingly important in structure-based drug design. Here, we describe the development of consensus Adaptation of Fields for Molecular Comparison (AFMoC) (abbreviated as AFMoCcon) models that account for multiple...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci7002472
更新日期：2007-11-01 00:00:00
abstract：:Advances in the development of high-throughput screening and automated chemistry have rapidly accelerated the production of chemical and biological data, much of them freely accessible through literature aggregator services such as ChEMBL and PubChem. Here, we explore how to use this comprehensive mapping of chemical ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00526
更新日期：2019-11-25 00:00:00
abstract：:We present our newly developed and highly efficient lossless compression algorithm for trajectories of atom positions and volumetric data. The algorithm is designed as a two-step approach. In the first step, efficient polynomial extrapolation schemes reduce the information entropy of the data by exploiting both spatia...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00501
更新日期：2018-10-22 00:00:00
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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：: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：:A generic chemical transformation may often be achieved under various synthetic conditions. However, for any specific reagents, only one or a few among the reported synthetic protocols may be successful. For example, Michael β-addition reactions may proceed under different choices of solvent (e.g., hydrophobic, aproti...
journal_title：Journal of chemical information and modeling
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更新日期：2015-02-23 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：: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：:A theoretical study of a variety of cyclohexane-based anion transporters interacting with the chloride anion has been conducted using density functional theory. The calculations have been performed in the gas phase but also, in order to describe the solvation effects on the interaction, two different solvents-chlorofo...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00154
更新日期：2019-05-28 00:00:00
abstract：:The COSMO surface polarization charge density σ resulting from quantum chemical calculations combined with a virtual conductor embedding has been widely proven to be a very suitable descriptor for the quantification of interactions of molecules in liquids. In a preceding paper, grid-based local histograms of σ have be...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300231t
更新日期：2012-08-27 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：:With the hope of discovering effective analgesics with fewer side effects, attention has recently shifted to allosteric modulators of the opioid receptors. In the past two years, the first chemotypes of positive or silent allosteric modulators (PAMs or SAMs, respectively) of μ- and δ-opioid receptor types have been re...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00388
更新日期：2015-09-28 00:00:00
abstract：:Inhibition of plasmin has been found to effectively reduce fibrinolysis and to avoid hemorrhage. This can be achieved by addressing its kringle 1 domain with the known drug and lysine analogue tranexamic acid. Guided by shape similarities toward a previously discovered lead compound, 5-(4-piperidyl)isoxazol-3-ol, a se...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00255
更新日期：2017-07-24 00:00:00
abstract：:Mass spectrometric data are copious and generate a processing burden that is best dealt with programmatically. PythoMS is a collection of tools based on the Python programming language that assist researchers in creating figures and video output that is informative, clear, and visually compelling. The PythoMS framewor...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00055
更新日期：2019-04-22 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：:Antimicrobial peptides (AMPs) have emerged as promising therapeutic alternatives to fight against the diverse infections caused by different pathogenic microorganisms. In this context, theoretical approaches in bioinformatics have paved the way toward the creation of several in silico models capable of predicting anti...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00630
更新日期：2016-03-28 00:00:00
abstract：:G-protein coupled receptors (GPCRs) are highly relevant drug targets. Four GPCRs with known crystal structure were analyzed with docking (AutoDock4) and postdocking (MM-PBSA) in order to evaluate the ability to recognize known antagonists from a larger database of molecular decoys and to predict correct binding modes....
journal_title：Journal of chemical information and modeling
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doi：10.1021/ci4000745
更新日期：2013-04-22 00:00:00
abstract：:Various cages are constructed by using three types of caps: f-cap (derived from spherical fullerenes by deleting zones of various size), kf-cap (obtainable by cutting off the polar ring, of size k), and t-cap ("tubercule"-cap). Building ways are presented, some of them being possible isomerization routes in the real c...
journal_title：Journal of chemical information and modeling
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doi：10.1021/ci049738g
更新日期：2005-03-01 00:00:00
abstract：:CYP19A1, also known as aromatase or estrogen synthetase, is the rate-limiting enzyme in the biosynthesis of estrogens from their corresponding androgens. Several clinically used breast cancer therapies target aromatase. In this work, explicitly solvated all-atom molecular dynamics simulations of aromatase with a model...
journal_title：Journal of chemical information and modeling
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doi：10.1021/ci400225w
更新日期：2013-08-26 00:00:00
abstract：:Finding a canonical ordering of the atoms in a molecule is a prerequisite for generating a unique representation of the molecule. The canonicalization of a molecule is usually accomplished by applying some sort of graph relaxation algorithm, the most common of which is the Morgan algorithm. There are known issues with...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00543
更新日期：2015-10-26 00:00:00
abstract：:The binding affinity and relative maximal efficacy of human A3 adenosine receptor (AR) agonists were each subjected to ligand-based three-dimensional quantitative structure-activity relationship analysis. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) used a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600501z
更新日期：2007-05-01 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：:Reaction classification has important applications, and many approaches to classification have been applied. Our own algorithm tests all maximum common substructures (MCS) between all reactant and product molecules in order to find an atom mapping containing the minimum chemical distance (MCD). Recent publications hav...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400442f
更新日期：2013-11-25 00:00:00
abstract：:A three-dimensional homology model of the human histamine H 4 receptor was developed to investigate the binding mode of a series of structurally diverse H 4-agonists, i.e. histamine, clozapine, and the recently described selective, nonimidazole agonist VUF 8430. Mutagenesis studies and docking of these ligands in a rh...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700474a
更新日期：2008-07-01 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：:Determination of structural similarities between protein binding pockets is an important challenge in in silico drug design. It can help to understand selectivity considerations, predict unexpected ligand cross-reactivity, and support the putative annotation of function to orphan proteins. To this end, Cavbase was dev...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5005898
更新日期：2015-01-26 00:00:00
