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 choices in ensemble-docking approaches for effective prediction of the binding geometry. Two study cases were selected in which binding involves different protein motions and intermolecular interactions and, accordingly, conformational selection and induced-fit mechanisms play different roles: binding of multiple ligands to the acetylcholine binding protein and highly specific binding of D-allose to the allose binding protein. Our results indicated that the ensemble-docking technique can provide reliable predictions of the structure of ligand-protein complexes, starting from simulations of the apo systems, when suitable methodological choices are made according to the different mechanistic scenarios. In particular, accelerated molecular dynamics simulations are suitable for conformational sampling when the unbound and bound states are separated by high energy barriers, provided that the acceleration parameters are carefully set to extensively sample the relevant conformations. A strategy specifically developed for geometric clustering of the binding site proved to be effective for selecting a set of conformations relevant to binding from the MD trajectory. Specific strategies have to be selected to incorporate different degrees of ligand-induced protein flexibility into the docking or pose-refinement steps.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Motta S,Bonati Ldoi
10.1021/acs.jcim.7b00125subject
Has Abstractpub_date
2017-07-24 00:00:00pages
1563-1578issue
7eissn
1549-9596issn
1549-960Xjournal_volume
57pub_type
杂志文章abstract：:When both the difference between two quantities and their individual values can be measured or computationally predicted, multiple quantities can be determined from the measurements or predictions of select individual quantities and select pairwise differences. These measurements and predictions form a network connect...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00528
更新日期：2019-11-25 00:00:00
abstract：:Arachidonic acid is an essential fatty acid in cells, acting as a key inflammatory intermediate in inflammatory reactions. In cardiac tissues, CYP2J2 can adopt arachidonic acid as a major substrate to produce epoxyeicosatrienoic acids (EETs), which can protect endothelial cells from ischemic or hypoxic injuries and ha...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400003p
更新日期：2013-06-24 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：: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：: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：:This article presents the computation of both inter- and intramolecular hydrogen bond strengths from first-principles. Quantum chemical calculations conducted at the dispersion-corrected density functional theory level including free energy and solvation contributions are conducted for (i) one-to-one hydrogen-bonded c...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00132
更新日期：2019-09-23 00:00:00
abstract：:With continually increased computer power, molecular mechanics force field-based approaches, such as the endpoint methods of molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) and molecular mechanics generalized Born surface area (MM-GBSA), have been routinely applied in both drug lead identification and opt...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00934
更新日期：2020-12-28 00:00:00
abstract：:Traditional herbal medicine has been an inseparable part of the traditional medical science in many countries throughout history. Nowadays, the popularity of using herbal medicines in daily life, as well as clinical practices, has gradually expanded to numerous Western countries with positive impacts and acceptance. T...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00826
更新日期：2020-03-23 00:00:00
abstract：:We introduce SARANEA, an open-source Java application for interactive exploration of structure-activity relationship (SAR) and structure-selectivity relationship (SSR) information in compound sets of any source. SARANEA integrates various SAR and SSR analysis functions and utilizes a network-like similarity graph data...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900416a
更新日期：2010-01-01 00:00:00
abstract：:Molecular docking can account for receptor flexibility by combining the docking score over multiple rigid receptor conformations, such as snapshots from a molecular dynamics simulation. Here, we evaluate a number of common snapshot selection strategies using a quality metric from stratified sampling, the efficiency of...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00314
更新日期：2018-09-24 00:00:00
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 a...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci600448b
更新日期：2007-05-01 00:00:00
abstract：:Given the essential role played by protein kinases in regulating cellular pathways, their dysregulation can result in the onset and/or progression of various human diseases. Structural analysis of diverse protein kinases suggests that these proteins exhibit a remarkable plasticity that allows them to adopt distinct co...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.7b00439
更新日期：2017-10-23 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 a departure from conventional chemical approaches, data-driven models of chemical reactions have recently been shown to be statistically successful using machine learning. These models, however, are largely black box in character and have not provided the kind of chemical insights that historically advanced the fie...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00721
更新日期：2020-03-23 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：:Due to the importance of hot-spots (HS) detection and the efficiency of computational methodologies, several HS detecting approaches have been developed. The current paper presents new models to predict HS for protein-protein and protein-nucleic acid interactions with better statistics compared with the ones currently...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500760m
更新日期：2015-05-26 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：: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：:Molecular fragment dynamics (MFD) is a variant of dissipative particle dynamics (DPD), a coarse-grained mesoscopic simulation technique for isothermal complex fuids and soft matter systems with particles that are chosen to be adequate fluid elements. MFD choses its particles to be small molecules which may be connecte...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5006096
更新日期：2015-05-26 00:00:00
abstract：:A new web portal for the CHARMM macromolecular modeling package, CHARMMing (CHARMM interface and graphics, http://www.charmming.org), is presented. This tool provides a user-friendly interface for the preparation, submission, monitoring, and visualization of molecular simulations (i.e., energy minimization, solvation,...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci800133b
更新日期：2008-09-01 00:00:00
abstract：:Protein-protein interactions play a key role in a multitude of biological processes, such as signal transduction, de novo drug design, immune responses, and enzymatic activities. It is of great interest to understand how proteins interact with each other. The general approach is to explore all possible poses and ident...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5002372
更新日期：2014-06-23 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：:Molecular fingerprints are widely used for similarity-based virtual screening in drug discovery projects. In this paper we discuss the performance and the complementarity of nine two-dimensional fingerprints (Daylight, Unity, AlFi, Hologram, CATS, TRUST, Molprint 2D, ChemGPS, and ALOGP) in retrieving active molecules ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0504723
更新日期：2006-05-01 00:00:00
abstract：:Machine learning has exhibited powerful capabilities in many areas. However, machine learning models are mostly database dependent, requiring a new model if the database changes. Therefore, a universal model is highly desired to accommodate the widest variety of databases. Fortunately, this universality may be achieve...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00878
更新日期：2019-05-28 00:00:00
abstract：:The evaluation of regression QSAR model performance, in fitting, robustness, and external prediction, is of pivotal importance. Over the past decade, different external validation parameters have been proposed: Q(F1)(2), Q(F2)(2), Q(F3)(2), r(m)(2), and the Golbraikh-Tropsha method. Recently, the concordance correlati...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci300084j
更新日期：2012-08-27 00:00:00
abstract：:HackaMol is an open source, object-oriented toolkit written in Modern Perl that organizes atoms within molecules and provides chemically intuitive attributes and methods. The library consists of two components: HackaMol, the core that contains classes for storing and manipulating molecular information, and HackaMol::X...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500359e
更新日期：2015-04-27 00:00:00
abstract：:The dissolution of a chemical into water is a process fundamental to both chemistry and biology. The persistence of a chemical within the environment and the effects of a chemical within the body are dependent primarily upon aqueous solubility. With the well-documented limitations hindering the accurate experimental d...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900286s
更新日期：2009-11-01 00:00:00
abstract：:Umami or the taste of monosodium glutamate represents one of the major attractive taste modalities in humans. Therefore, knowledge about biophysical and biochemical properties of the umami taste is important for both scientific research and the food industry. Experimental approaches for predicting umami peptides are l...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00707
更新日期：2020-12-28 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：:Homology modeling is a reliable method of predicting the three-dimensional structures of proteins that lack NMR or X-ray crystallographic data. It employs the assumption that a structural resemblance exists between closely related proteins. Despite the availability of many crystal structures of possible templates, onl...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500001f
更新日期：2014-06-23 00:00:00
