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. A variety of approaches/tools to compute and interrogate hydration properties in structural ensembles of proteins, nucleic acids, or in general any molecule are available and are complemented here with a new and free software package ("JAL"). Central to "JAL" is an intuitive atom centric approach of computing hydration properties. In addition to the standard metrics commonly used to understand hydration, "JAL" introduces two nonstandard utilities: a program to rapidly compute buried waters in an MD trajectory and a new method to compute multiwater bridges around a solute. We demonstrate the utility of the package by probing the hydration characteristics of the tumor suppressor protein p53 and the translation initiation factor eif4E. "JAL" is hosted online and can be accessed for free at http://mspc.bii.a-star.edu.sg/minhn/jal.html .
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Pradhan MR,Nguyen MN,Kannan S,Fox SJ,Kwoh CK,Lane DP,Verma CSdoi
10.1021/acs.jcim.8b00453subject
Has Abstractpub_date
2019-07-22 00:00:00pages
3316-3329issue
7eissn
1549-9596issn
1549-960Xjournal_volume
59pub_type
杂志文章abstract：:Scoring the activity of compounds in phenotypic high-throughput assays presents a unique challenge because of the limited resolution and inherent measurement error of these assays. Techniques that leverage the structural similarity of compounds within an assay can be used to improve the hit-recovery rate from screenin...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci050087d
更新日期：2005-11-01 00:00:00
abstract：:Molecular dynamics simulations provide valuable insights into the behavior of molecular systems. Extending the recent trend of using machine learning techniques to predict physicochemical properties from molecular dynamics data, we propose to consider the trajectories as multidimensional time series represented by 2D ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00135
更新日期：2019-08-26 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：:Histone deacetylases (HDACs) are an important class of drug targets for the treatment of cancers, neurodegenerative diseases, and other types of diseases. Virtual screening (VS) has become fairly effective approaches for drug discovery of novel and highly selective histone deacetylase inhibitors (HDACIs). To facilitat...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci5005515
更新日期：2015-02-23 00:00:00
abstract：:The emergence of a large amount of pharmacological, genomic, and network knowledge data provides new challenges and opportunities for drug discovery and development. Identification of real small-molecule drug (SM)-miRNA associations is not only important in the development of effective drug repositioning but also cruc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00244
更新日期：2020-08-24 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：:The ligand binding determinants for the angiotensin II type 1 receptor (AT1R), a G protein-coupled receptor (GPCR), have been characterized by means of computer simulations. As a first step, a pharmacophore model of various known AT1R ligands exhibiting a wide range of binding affinities was generated. Second, a struc...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci400400m
更新日期：2013-11-25 00:00:00
abstract：:This paper presents an exploratory study of a novel method for flexible 3-D similarity searching based on autocorrelation vectors and smoothed bounded distance matrices. Although the new approach is unable to outperform an existing 2-D similarity searching in terms of enrichment factors, it is able to retrieve differe...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci0503863
更新日期：2006-03-01 00:00:00
abstract：:Reversible covalent inhibitors have drawn increasing attention in drug design, as they are likely more potent than noncovalent inhibitors and less toxic than covalent inhibitors. Despite those advantages, the computational prediction of reversible covalent binding presents a formidable challenge because the binding pr...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00959
更新日期：2019-05-28 00:00:00
abstract：:The cannabinoid receptor subtype 2 (CB2) is a promising therapeutic target for blood cancer, pain relief, osteoporosis, and immune system disease. The recent withdrawal of Rimonabant, which targets another closely related cannabinoid receptor (CB1), accentuates the importance of selectivity for the development of CB2 ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci3003914
更新日期：2013-01-28 00:00:00
abstract：:The human DNA-repair O (6)-alkylguanine DNA alkyltransferase (MGMT or hAGT) protein protects DNA from environmental alkylating agents and also plays an important role in tumor resistance to chemotherapy treatment. Available inhibitors, based on pseudosubstrate analogs, have been shown to induce substantial bone marrow...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700447r
更新日期：2008-04-01 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：: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 SZMAP method computes binding free energies and the corresponding thermodynamic components for water molecules in the binding site of a protein structure [ SZMAP, 1.0.0 ; OpenEye Scientific Software Inc. : Santa Fe, NM, USA , 2011 ]. In this work, the ability of SZMAP to predict water structure and thermodynamic s...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci500746d
更新日期：2015-08-24 00:00:00
abstract：:Reaction databases provide a great deal of useful information to assist planning of experiments but do not provide any interpretation or chemical concepts to accompany this information. In this work, reactions are labeled with experimental conditions, and network analysis shows that consistencies within clusters of da...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00313
更新日期：2019-09-23 00:00:00
abstract：:We have studied the binding affinities of a set of 45 small-molecule inhibitors to protein tyrosine phosphatase 1B (PTP1B) through computational approaches. All of these compounds share a common oxalylamino benzoic acid (OBA) moiety. The complex structure of each compound was modeled by using the GOLD program plus the...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci8004429
更新日期：2009-04-01 00:00:00
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 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：:The failure of default scoring functions to ensure virtual screening enrichment is a persistent problem for the molecular docking algorithms used in structure-based drug discovery. To remedy this problem, elaborate rescoring and postprocessing schemes have been developed with a varying degree of success, specificity, ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00383
更新日期：2019-08-26 00:00:00
abstract：:In this study, we have developed a two model system to mimic the active and inactive states of a G-protein coupled receptor specifically the alpha1A adrenergic receptor. We have docked two agonists, epinephrine (phenylamine type) and oxymetazoline (imidazoline type), as well as two antagonists, prazosin and 5-methylur...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci700026v
更新日期：2007-09-01 00:00:00
abstract：:We report here on long-time all-atomistic molecular dynamics simulations of functional supramolecular nanotubes composed by the self-assembly of peptide-drug amphiphiles (DAs). These DAs have been shown to possess an inherently high drug loading of the hydrophobic anticancer drug camptothecin. We probe the self-assemb...
journal_title：Journal of chemical information and modeling
pub_type： 信件
doi：10.1021/acs.jcim.8b00193
更新日期：2018-06-25 00:00:00
abstract：:Membrane transporters play a crucial role in determining fate of administered drugs in a biological system. Early identification of plausible transporters for a drug molecule can provide insights into its therapeutic, pharmacokinetic, and toxicological profiles. In the present study, predictive models for classifying ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.6b00508
更新日期：2017-03-27 00:00:00
abstract：:Moving to a new country, with a different culture and a new environment, is not an easy decision. In this perspective, I present some reasons that made me, a Brazilian computational biochemist, move abroad to do postdoctoral research and some of the challenges I faced before and after moving. ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.9b00764
更新日期：2020-02-24 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：: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：: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：:Insect neuropeptide receptors, including allatostatin receptor type C (AstR-C), a G protein-coupled receptor, are among the potential targets for designing next-generation pesticides that despite their importance in offering a new mode-of-action have been overlooked. Focusing on AstR-C of Thaumetopoea pityocampa, a co...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.0c00985
更新日期：2021-01-21 00:00:00
abstract：:Alanine scanning is a tool in molecular biology that is commonly used to evaluate the contribution of a specific amino acid residue to the stability and function of a protein. Additionally, this tool is also used to understand whether the side chain of a specific amino acid residue plays a role in the protein's bioact...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/acs.jcim.8b00926
更新日期：2019-02-25 00:00:00
abstract：:TAMkin is a program for the calculation and analysis of normal modes, thermochemical properties and chemical reaction rates. At present, the output from the frequently applied software programs ADF, CHARMM, CPMD, CP2K, Gaussian, Q-Chem, and VASP can be analyzed. The normal-mode analysis can be performed using a broad ...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci100099g
更新日期：2010-09-27 00:00:00
abstract：:To discover non-nucleoside inhibitors of HIV-1 reverse transcriptase (NNRTIs) that are effective against both wild-type (WT) virus and variants that encode the clinically troublesome Tyr181Cys (Y181C) RT mutation, virtual screening by docking was carried out using three RT structures and more than 2 million commercial...
journal_title：Journal of chemical information and modeling
pub_type： 杂志文章
doi：10.1021/ci900068k
更新日期：2009-05-01 00:00:00
