Abstract：
:Mapping the chemical space of small organic molecules is approached from a theoretical graph theory viewpoint, in an effort to begin the systematic exploration of molecular topologies. We present an algorithm for exhaustive generation of scaffold topologies with up to eight rings and an efficient comparison method for graphs within this class. This method uses the return index, a topological invariant derived from the adjacency matrix of the graph. Furthermore, we describe an algorithm that verifies the adequacy of the comparison method. Applications of this method for chemical space exploration in the context of drug discovery are discussed. The key result is a unique characterization of scaffold topologies, which may lead to more efficient ways to query large chemical databases.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Pollock SN,Coutsias EA,Wester MJ,Oprea TIdoi
10.1021/ci7003412subject
Has Abstractpub_date
2008-07-01 00:00:00pages
1304-10issue
7eissn
1549-9596issn
1549-960Xjournal_volume
48pub_type
杂志文章abstract：:The primary goal of ligand-based virtual screening is to identify active compounds consisting of a core scaffold that is not found in the current active compound pool. Scaffold hopping is the term used for this purpose. In the present study, topological representations of pharmacophore features on chemical graphs were...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00098
更新日期：2020-04-27 00:00:00
abstract：:The appropriate selection of a chemical space represented by the data set, the selection of its chemical data representation, the development of a correct modeling process using a robust and reproducible algorithm, and the performance of an exhaustive training and external validation determine the usability and reprod...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00492
更新日期：2017-11-27 00:00:00
abstract：:Side-chain modeling is critical for protein structure prediction since the uniqueness of the protein structure is largely determined by its side-chain packing conformation. In this paper, differing from most approaches that rely on rotamer library sampling, we first propose a novel side-chain rotamer prediction method...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00951
更新日期：2020-12-28 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：:Selecting a small subset of descriptors from a large pool to build a predictive quantitative structure-activity relationship (QSAR) model is an important step in the QSAR modeling process. In general, subset selection is very hard to solve, even approximately, with guaranteed performance bounds. Traditional approaches...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600563w
更新日期：2007-05-01 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：:We introduce the statistics behind a novel type of SAR analysis named "nonadditivity analysis". On the basis of all pairs of matched pairs within a given data set, the approach analyzes whether the same transformations between related molecules have the same effect, i.e., whether they are additive. Assuming that the e...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00631
更新日期：2019-09-23 00:00:00
abstract：:We used synthetic peloruside A for the commercial preparation of [³H]peloruside A. The radiolabeled compound bound to preformed tubulin polymer in amounts stoichiometric with the polymer's tubulin content, with an apparent K(d) value of 0.35 μM. A less active peloruside A analogue, (11-R)-peloruside A and laulimalide ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci1002894
更新日期：2010-11-22 00:00:00
abstract：:An accurate scoring function is expected to correctly select the most stable structure from a set of pose candidates. One can hypothesize that a scoring function's ability to identify the most stable structure might be improved by emphasizing the most relevant atom pairwise interactions. However, it is hard to evaluat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00356
更新日期：2019-07-22 00:00:00
abstract：:Engineering shape-controlled bionanomaterials requires comprehensive understanding of interactions between biomolecules and inorganic surfaces. We explore the origin of facet-selective binding of peptides adsorbed onto Pt(100) and Pt(111) crystallographic planes. Using molecular dynamics simulations, we show that upon...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400630d
更新日期：2013-12-23 00:00:00
abstract：:DiSCuS, a "Database System for Compound Selection", has been developed. The primary goal of DiSCuS is to aid researchers in the steps subsequent to generating high-throughput virtual screening (HTVS) results, such as selection of compounds for further study, purchase, or synthesis. To do so, DiSCuS provides (1) a stor...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400587f
更新日期：2014-01-27 00:00:00
abstract：:HIV-1 replication requires binding to occur between Trans-activation Response Element (TAR) RNA and the TAT protein. This TAR-TAT binding depends on the conformation of TAR, and therapeutic development has attempted to exploit this dynamic behavior. Here we simulate TAR dynamics in the context of mutations inhibiting ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00152
更新日期：2016-09-26 00:00:00
abstract：:Large corpora of kinase small molecule inhibitor data are accessible to public sector research from thousands of journal article and patent publications. These data have been generated employing a wide variety of assay methodologies and experimental procedures by numerous laboratories. Here we ask the question how app...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300403k
更新日期：2013-01-28 00:00:00
abstract：:A novel approach was developed to rationally interface structure- and ligand-based drug design through the rescoring of docking poses and automated generation of molecular alignments for 3D quantitative structure-activity relationship investigations. The procedure was driven by a genetic algorithm optimizing the value...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800015s
更新日期：2008-06-01 00:00:00
abstract：:Aminoglycosides are antibiotics targeting the 16S RNA A site of the bacterial ribosome. There have been many efforts directed toward design of their synthetic derivatives, however with only few successes. As RNA binders, aminoglycosides are also a difficult target for computational drug design, since most of the exist...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800361a
更新日期：2009-02-01 00:00:00
abstract：:Structure-based virtual screening is highly used in the early stages of drug discovery to identify new putative lead compounds for a given target. However, when a small molecule elicits a biological effect, but its target is unknown, or the side effects it causes arise from its undesired interaction with unknown count...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00428
更新日期：2019-11-25 00:00:00
abstract：:The α2a adrenoceptor is a medically relevant subtype of the G protein-coupled receptor family. Unfortunately, high-throughput techniques aimed at producing novel drug leads for this receptor have been largely unsuccessful because of the complex pharmacology of adrenergic receptors. As such, cutting-edge in silico liga...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c01019
更新日期：2021-01-25 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：:Protein dynamics play a critical role in ligand binding, and different models have been proposed to explain the relationships between protein motion and molecular recognition. Here, we present a study of ligand-binding processes associated with large conformational changes of a protein to elucidate the critical choice...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00125
更新日期：2017-07-24 00:00:00
abstract：:A compound's synthetic accessibility (SA) is an important aspect of drug design, since in some cases computer-designed compounds cannot be synthesized. There have been several reports on SA prediction, most of which have focused on the difficulties of synthetic reactions based on retro-synthesis analyses, reaction dat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500568d
更新日期：2014-12-22 00:00:00
abstract：:Metal-ligand (M-L) bond lengths for a range of ligands (carboxylates, chlorides, pyridines, water, tertiary phosphines, and alkenes) and a variety of metals have been retrieved from the Cambridge Structural Database, CSD. Analysis of the factors which affect M-L bond lengths (for example, ligand coordination mode, oxi...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0500785
更新日期：2005-11-01 00:00:00
abstract：:The purpose of this investigation is to contribute to the development of new anticonvulsant drugs to treat patients with refractory epilepsy. We applied a virtual screening protocol that involved the search into molecular databases of new compounds and known drugs to find small molecules that interact with the open co...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00721
更新日期：2018-07-23 00:00:00
abstract：:Herein we present the VMD Store, an open-source VMD plugin that simplifies the way that users browse, discover, install, update, and uninstall extensions for the Visual Molecular Dynamics (VMD) software. The VMD Store obtains data about all the indexed VMD extensions hosted on GitHub and presents a one-click mechanism...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00739
更新日期：2019-11-25 00:00:00
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：: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：: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：:With chemical libraries increasingly containing millions of compounds or more, there is a fast-growing need for computational methods that can rank or prioritize compounds for screening. Machine learning methods have shown considerable promise for this task; indeed, classification methods such as support vector machin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci9003865
更新日期：2010-05-24 00:00:00
abstract：:Pharmacophore search is a key component of many drug discovery efforts. Pharmer is a new computational approach to pharmacophore search that scales with the breadth and complexity of the query, not the size of the compound library being screened. Two novel methods for organizing pharmacophore data, the Pharmer KDB-tre...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200097m
更新日期：2011-06-27 00:00:00
abstract：:Novel statistical potentials derived from known protein structures are presented. They are designed to describe cation-pi and amino-pi interactions between a positively charged amino acid or an amino acid carrying a partially charged amino group and an aromatic moiety. These potentials are based on the propensity of r...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050395b
更新日期：2006-03-01 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
