Abstract：
:Computer-aided drug design methods such as docking, pharmacophore searching, 3D database searching, and the creation of 3D-QSAR models need conformational ensembles to handle the flexibility of small molecules. Here, we present Conformator, an accurate and effective knowledge-based algorithm for generating conformer ensembles. With 99.9% of all test molecules processed, Conformator stands out by its robustness with respect to input formats, molecular geometries, and the handling of macrocycles. With an extended set of rules for sampling torsion angles, a novel algorithm for macrocycle conformer generation, and a new clustering algorithm for the assembly of conformer ensembles, Conformator reaches a median minimum root-mean-square deviation (measured between protein-bound ligand conformations and ensembles of a maximum of 250 conformers) of 0.47 Å with no significant difference to the highest-ranked commercial algorithm OMEGA and significantly higher accuracy than seven free algorithms, including the RDKit DG algorithm. Conformator is freely available for noncommercial use and academic research.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Friedrich NO,Flachsenberg F,Meyder A,Sommer K,Kirchmair J,Rarey Mdoi
10.1021/acs.jcim.8b00704subject
Has Abstractpub_date
2019-02-25 00:00:00pages
731-742issue
2eissn
1549-9596issn
1549-960Xjournal_volume
59pub_type
杂志文章abstract：:Aβ25-35 is a short, cytotoxic, and naturally occurring fragment of the Alzheimer's Aβ peptide. To map the molecular mechanism of Aβ25-35 binding to the zwitterionic dimyristoylphosphatidylcholine (DMPC) bilayer, we have performed replica exchange with solute tempering molecular dynamics simulations using all-atom expl...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00045
更新日期：2018-05-29 00:00:00
abstract：:G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors, which is arguably the most important family of drug target. With the technology breakthroughs in X-ray crystallography and cryo-electron microscopy, more than 300 GPCR-ligand complex structures have been publicly reported since 2007,...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00699
更新日期：2020-09-28 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：:A novel pharmacophore descriptor Flexophore is presented, which considers molecular flexibility when comparing descriptor similarities. The descriptor is a complete reduced graph of the underlying molecule. Its nodes are represented by enhanced MM2 atom types, while the edge descriptions encode the molecular flexibili...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700359j
更新日期：2008-04-01 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：:We present a theoretical study on the performance of ensemble docking methodologies considering multiple protein structures. We perform a theoretical analysis of pose prediction experiments which is completely unbiased, as we make no assumptions about specific scoring functions, search paradigms, protein structures, o...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci2002796
更新日期：2011-11-28 00:00:00
abstract：:We propose predictive performance criteria for nonlinear regression models without cross-validation. The proposed criteria are the determination coefficient and the root-mean-square error for the midpoints between k-nearest-neighbor data points. These criteria can be used to evaluate predictive ability after the regre...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci4003766
更新日期：2013-09-23 00:00:00
abstract：:Deep learning has drawn significant attention in different areas including drug discovery. It has been proposed that it could outperform other machine learning algorithms, especially with big data sets. In the field of pharmaceutical industry, machine learning models are built to understand quantitative structure-acti...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00671
更新日期：2019-03-25 00:00:00
abstract：:Whereas 400 million distinct compounds are now purchasable within the span of a few weeks, the biological activities of most are unknown. To facilitate access to new chemistry for biology, we have combined the Similarity Ensemble Approach (SEA) with the maximum Tanimoto similarity to the nearest bioactive to predict a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00316
更新日期：2018-01-22 00:00:00
abstract：:SIRT2, which is a NAD+ (nicotinamide adenine dinucleotide) dependent deacetylase, has been demonstrated to play an important role in the occurrence and development of a variety of diseases such as cancer, ischemia-reperfusion, and neurodegenerative diseases. Small molecule inhibitors of SIRT2 are thought to be potenti...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00714
更新日期：2017-04-24 00:00:00
abstract：:The metabolism of xenobiotics--and more specifically drugs--in the liver is a critical process controlling their half-life. Although there exist experimental methods, which measure the metabolic stability of xenobiotics and identify their metabolites, developing higher throughput predictive methods is an avenue of res...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci3003073
更新日期：2012-09-24 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：:We describe a general methodology for designing an empirical scoring function and provide smina, a version of AutoDock Vina specially optimized to support high-throughput scoring and user-specified custom scoring functions. Using our general method, the unique capabilities of smina, a set of default interaction terms ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300604z
更新日期：2013-08-26 00:00:00
abstract：:The in silico prediction of unwanted side effects (SEs) caused by the promiscuous behavior of drugs and their targets is highly relevant to the pharmaceutical industry. Considerable effort is now being put into computational and experimental screening of several suspected off-target proteins in the hope that SEs might...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00120
更新日期：2015-09-28 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：:Computational approaches to fragment-based drug design (FBDD) can complement experiments and facilitate the identification of potential hot spots along the protein surface. However, the evaluation of computational methods for mapping binding sites frequently focuses upon the ability to reproduce crystallographic coord...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300430v
更新日期：2013-02-25 00:00:00
abstract：:A comprehensive safety evaluation of chemicals should require toxicity assessment in both the aquatic and terrestrial test species. Due to the application practices and nature of chemical pesticides, the avian toxicity testing is considered as an essential requirement in the risk assessment process. In this study, tre...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00139
更新日期：2015-07-27 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
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：:Designing organic saccharide sensors for use in aqueous solution is a nontrivial endeavor. Incorporation of hydrogen bonding groups on a sensor's receptor unit to target saccharides is an obvious strategy but not one that is likely to ensure analyte-receptor interactions over analyte-solvent or receptor-solvent intera...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00987
更新日期：2019-05-28 00:00:00
abstract：:Spin diffusion is a formidable problem when interpreting NMR data of chemical compounds. We developed a method to reconstruct the conformational ensemble of flexible molecules displaying spin diffusion, which minimizes the subjective bias in the interpretation of experimental data and which can be used routinely to ob...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00259
更新日期：2019-06-24 00:00:00
abstract：:Acetohydroxyacid synthase (AHAS) is a thiamin diphosphate-dependent enzyme involved in the biosynthesis of valine, leucine, isoleucine, and lysine. Experimental evidence has shown that mutation of the Gln202 residue results in a decrease in the enzymatic activity, thus suggesting the main role of the carboligation cat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00863
更新日期：2020-02-24 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：:Angiotensin II type 1 receptor (AT1R) is the principal regulator of blood pressure in humans. The overactivation of AT1R by the stimulation of angiotensin II would result in high blood pressure. To prevent hypertension, nonpeptide "sartan" drugs, such as valsartan (VST), have been developed to competitively block the ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00364
更新日期：2018-10-22 00:00:00
abstract：:Our recent studies show that the single Tyr residue in the sequence of amyloid-β42 (Aβ42) is reactive toward various ligands, including metals and adenosine trisphospate (see: Coskuner , O. J. Biol. Inorg. Chem. 2016 , 21 , 957 - 973 and Coskuner , O. ; Murray , I. V. J. J. Alzheimer's Dis. 2014 , 41 , 561 - 574 ). Ho...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00761
更新日期：2017-06-26 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：: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：:Naturally occurring anticancer compounds represent about half of the chemotherapeutic drugs which have been put in the market against cancer until date. Computer-based or in silico virtual screening methods are often used in lead/hit discovery protocols. In this study, the "drug-likeness" of ~400 compounds from Africa...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5003697
更新日期：2014-09-22 00:00:00
abstract：:The human cytochrome P450 (CYP450) isozymes are the most important enzymes in the body to metabolize many endogenous and exogenous substances including environmental toxins and therapeutic drugs. Any unnecessary interactions between a small molecule and CYP450 isozymes may raise a potential to disarm the integrity of ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci200311w
更新日期：2011-10-24 00:00:00
abstract：:Cytochrome P450 2D6 (CYP2D6) is used to develop an approach for predicting affinity and relevant binding conformation(s) for highly flexible binding sites. The approach combines the use of docking scores and compound properties as attributes in building a neural network (NN) model. It begins by identifying segments of...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600267k
更新日期：2006-11-01 00:00:00
