Abstract：
:Understanding the relationship between chemical structure and function is a ubiquitous problem within the fields of chemistry and biology. Simulation approaches attack the problem utilizing physics to understand a given process at the particle level. Unfortunately, these approaches are often too expensive for many problems of interest. Informatics approaches attack the problem with empirical analysis of descriptions of chemical structure. The issue in these methods is how to describe molecules in a manner that facilitates accurate and general calculation of molecular properties. Here, we present a novel approach that utilizes aspects of simulation and informatics in order to formulate structure-property relationships. We show how supervised learning can be utilized to overcome the sampling problem in simulation approaches. Likewise, we show how learning can be achieved based on molecular descriptions that are rooted in the physics of dynamic intermolecular forces. We apply the approach to three problems including the analysis of corticosteroid binding globulin ligand binding affinity, identification of formylpeptide receptor ligands, and identification of resveratrol analogues capable of inhibiting activation of transcription factor nuclear factor kappaB.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Brown WM,Sasson A,Bellew DR,Hunsaker LA,Martin S,Leitao A,Deck LM,Vander Jagt DL,Oprea TIdoi
10.1021/ci8001233subject
Has Abstractpub_date
2008-08-01 00:00:00pages
1626-37issue
8eissn
1549-9596issn
1549-960Xjournal_volume
48pub_type
杂志文章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：:Pharmacophore patterns in ligands can be effectively characterized in terms of their constituent pharmacophore multiplets. Bitsets (fingerprints) encoding which particular multiplets are found in a given ligand have been and continue to be used as molecular descriptors in a range of molecular modeling applications, fr...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800234q
更新日期：2008-12-01 00:00:00
abstract：:The number of journal articles in the scientific domain has grown to the point where it has become impossible for researchers to capitalize on all findings in their relevant discipline. Information is stored in these articles in a number of ways, including figures that describe important results. In organic chemistry,...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00042
更新日期：2020-04-27 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：: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：:Most of the common molecular descriptors have numerous different implementations. This can influence the results of compound prioritization based on the multiparameter assessment (MPA) approach that allows a medicinal chemist to simultaneously analyze and achieve the desired balance of the diverse and often conflictin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00734
更新日期：2018-05-29 00:00:00
abstract：:Partial covalent interactions (PCIs) in proteins, which include hydrogen bonds, salt bridges, cation-π, and π-π interactions, contribute to thermodynamic stability and facilitate interactions with other biomolecules. Several score functions have been developed within the Rosetta protein modeling framework that identif...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00398
更新日期：2018-05-29 00:00:00
abstract：:Prediction of compound properties from structure via quantitative structure-activity relationship and machine-learning approaches is an important computational chemistry task in small-molecule drug research. Though many such properties are dependent on three-dimensional structures or even conformer ensembles, the majo...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00151
更新日期：2018-05-29 00:00:00
abstract：:In this paper, we introduce the BiKi Life Sciences suite. This software makes it easy for computational medicinal chemists to run ad hoc molecular dynamics protocols in a novel and task-oriented environment; as a notebook, BiKi (acronym of Binding Kinetics) keeps memory of any activity together with dependencies among...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00680
更新日期：2018-02-26 00:00:00
abstract：:Cryo-electron microscopy (cryo-EM) is emerging as a real alternative for structural elucidation. In spite of this, very few cryo-EM structures have been described so far as successful platforms for in silico drug design. Gabapentin and pregabalin are some of the most successful drugs in the treatment of epilepsy and n...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00347
更新日期：2018-08-27 00:00:00
abstract：:Sterol 14α-demethylase (CYP51) is the main drug target for the treatment of fungal infections. The discovery of new efficient fungal CYP51 inhibitors requires an understanding of the structural requirements for selectivity for the fungal over the human ortholog. In this study, a binding mode of the pyridylethanol(phen...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500556k
更新日期：2014-12-22 00:00:00
abstract：:Protein-ligand (PL) interactions play a key role in many life processes such as molecular recognition, molecular binding, signal transmission, and cell metabolism. Examples of interaction forces include hydrogen bonding, hydrophobic effects, steric clashes, electrostatic contacts, and van der Waals attractions. Curren...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00310
更新日期：2018-01-22 00:00:00
abstract：:This study examines the dependence of molecular alignment accuracy on a variety of factors including the choice of molecular template, alignment method, conformational flexibility, and type of protein target. We used eight test systems for which X-ray data on 145 ligand-protein complexes were available. The use of X-r...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci060134h
更新日期：2006-09-01 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 in silico screening procedure was performed to select new inhibitors of glycogen synthase kinase 3β (GSK-3β), a serine/threonine protein kinase that in the last two decades has emerged as a key target in drug discovery, having been implicated in multiple cellular processes and linked with the pathogenesis of severa...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.5b00486
更新日期：2015-12-28 00:00:00
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：: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 a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci7003384
更新日期：2008-03-01 00:00:00
abstract：:We present a succession of structural changes involved in hormone peptide activation of a prototypical GPCR. Microsecond molecular dynamics simulation generated conformational ensembles reveal propagation of structural changes through key "microswitches" within human AT1R bound to native hormone. The endocrine octa-pe...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00583
更新日期：2019-01-28 00:00:00
abstract：:Structure-based virtual screening relies on classical scoring functions that often fail to reliably discriminate binders from nonbinders. In this work, we present a high-throughput protein-ligand complex molecular dynamics (MD) simulation that uses the output from AutoDock Vina to improve docking results in distinguis...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00057
更新日期：2020-04-27 00:00:00
abstract：:Virtual screening (VS) can be accomplished in either ligand- or structure-based methods. In recent times, an increasing number of 2D fingerprint and 3D shape similarity methods have been used in ligand-based VS. To evaluate the performance of these ligand-based methods, retrospective VS was performed on a tailored dir...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300030u
更新日期：2012-05-25 00:00:00
abstract：:Many of the conventional similarity methods assume that molecular fragments that do not relate to biological activity carry the same weight as the important ones. One possible approach to this problem is to use the Bayesian inference network (BIN), which models molecules and reference structures as probabilistic infer...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100232h
更新日期：2011-01-24 00:00:00
abstract：:A comprehensive data set of aligned ligands with highly similar binding pockets from the Protein Data Bank has been built. Based on this data set, a scoring function for recognizing good alignment poses for small molecules has been developed. This function is based on atoms and hydrogen-bond projected features. The co...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100227h
更新日期：2010-09-27 00:00:00
abstract：:A MMGBSA variant (here referred to as Nwat-MMGBSA), based on the inclusion of a certain number of explicit water molecules (Nwat) during the calculations, has been tested on a set of 20 protein-protein complexes, using the correlation between predicted and experimental binding energy as the evaluation metric. Besides ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00196
更新日期：2016-09-26 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
abstract：:Engineered nanomaterials (ENMs) are increasingly infiltrating our lives as a result of their applications across multiple fields. However, ENM formulations may result in the modulation of pathways and mechanisms of toxic action that endanger human health and the environment. Alternative testing methods such as in sili...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00223
更新日期：2017-09-25 00:00:00
abstract：:Optimization of ligand binding affinity to the target protein of interest is a primary objective in small-molecule drug discovery. Until now, the prediction of binding affinities by computational methods has not been widely applied in the drug discovery process, mainly because of its lack of accuracy and reproducibili...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00780
更新日期：2017-04-24 00:00:00
abstract：:Identifying drug-target interactions (DTIs) plays an important role in the field of drug discovery, drug side-effects, and drug repositioning. However, in vivo or biochemical experimental methods for identifying new DTIs are extremely expensive and time-consuming. Recently, in silico or various computational methods h...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00408
更新日期：2019-07-22 00:00:00
abstract：:While critically reviewing the current status of what is known about C28H14 and C30H14 benzenoid isomers, which are ubiquitous pyrolytic constituents, some new insights will be presented. Representative isomers belonging to these benzenoid hydrocarbons are at the crossroads to homologous series that extend to infinite...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050298i
更新日期：2006-03-01 00:00:00
abstract：:ThermoData Engine (TDE) is the first full-scale software implementation of the dynamic data evaluation concept, as reported in this journal. The present article describes the background and implementation for new additions in latest release of TDE. Advances are in the areas of program architecture and quality improvem...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci4005699
更新日期：2013-12-23 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
