Abstract:
:Increased reports of oseltamivir (OTV)-resistant strains of the influenza virus, such as the H274Y mutation on its neuraminidase (NA), have created some cause for concern. Many studies have been conducted in the attempt to uncover the mechanism of OTV resistance in H274Y NA. However, most of the reported studies on H274Y focused only on the drug-bound system, so the direct effects of the mutation on NA itself prior to drug binding still remain unclear. Therefore, molecular dynamics simulations of NA in apo form, followed by principal component analysis and interaction energy calculations, were performed to investigate the structural changes of the NA binding site as a result of the H274Y mutation. It was observed that the disruption of the NA binding site due to the H274Y mutation was initiated by the repulsive effect of Y274 on the 250-loop, which in turn altered the hydrogen-bonding network around residue 274. The rotated W295 side chain caused the upward movement of the 340-loop. Consequently, sliding box docking results suggested that the binding pathway of OTV was compromised because of the disruption of this binding site. This study also highlighted the importance of the functional group at C6 of the sialic acid mimicry. It is hoped that these results will improve the understanding of OTV resistance and shed some light on the design of a novel anti-influenza drug.
journal_name
J Chem Inf Modeljournal_title
Journal of chemical information and modelingauthors
Yusuf M,Mohamed N,Mohamad S,Janezic D,Damodaran KV,Wahab HAdoi
10.1021/acs.jcim.5b00331subject
Has Abstractpub_date
2016-01-25 00:00:00pages
82-100issue
1eissn
1549-9596issn
1549-960Xjournal_volume
56pub_type
杂志文章abstract::The high-throughput docking protocol called ALTA-VS (anchor-based library tailoring approach for virtual screening) was developed in 2005 for the efficient in silico screening of large libraries of compounds by preselection of only those molecules that have optimal fragments (anchors) for the protein target. Here we p...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00336
更新日期:2017-10-23 00:00:00
abstract::Big data is one of the key transformative factors which increasingly influences all aspects of modern life. Although this transformation brings vast opportunities it also generates novel challenges, not the least of which is organizing and searching this data deluge. The field of medicinal chemistry is not different: ...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00249
更新日期:2017-08-28 00:00:00
abstract::The importance of thorough analyses of the secondary structures in proteins as basic structural units cannot be overemphasized. Although recent computational methods have achieved reasonably high accuracy for predicting secondary structures from amino acid sequences, a simple and fundamental empirical approach to char...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci900452z
更新日期:2010-04-26 00:00:00
abstract::We describe here our tool named PyPLIF HIPPOS, which was newly developed to analyze the docking results of AutoDock Vina and PLANTS. Its predecessor, PyPLIF (https://github.com/radifar/pyplif), is a molecular interaction fingerprinting tool for the docking results of PLANTS, exclusively. Unlike its predecessor, PyPLIF...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00305
更新日期:2020-08-24 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::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::Although there are several databases that contain data on many metabolites and reactions in biochemical pathways, there is still a big gap in the numbers between experimentally identified enzymes and metabolites. It is supposed that many catalytic enzyme genes are still unknown. Although there are previous studies tha...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.5b00216
更新日期:2016-03-28 00:00:00
abstract::Blockade of human ether-à-go-go related gene (hERG) channel prolongs the duration of the cardiac action potential and is a common reason for drug failure in preclinical safety trials. Therefore, it is of great importance to develop robust in silico tools to predict potential hERG blockers in the early stages of drug d...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200271d
更新日期:2011-11-28 00:00:00
abstract::Inhibitors of histone deacetylases (HDACIs) have emerged as a new class of drugs for the treatment of human cancers and other diseases because of their effects on cell growth, differentiation, and apoptosis. In this study we have developed several quantitative structure-activity relationship (QSAR) models for 59 chemi...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci800366f
更新日期:2009-02-01 00:00:00
abstract::Universal generative topographic maps (GTMs) provide two-dimensional representations of chemical space selected for their "polypharmacological competence", that is, the ability to simultaneously represent meaningful activity and property landscapes, associated with many distinct targets and properties. Several such GT...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.8b00650
更新日期:2019-01-28 00:00:00
abstract::We present an algorithm, ReFlex3D, for the refinement of flexible molecular alignments based on their three-dimensional shape and electrostatic properties. The algorithm is designed to be used with fast conformer generators to refine an initial overlay between two molecules and thus to obtain improved overlaps as judg...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00618
更新日期:2018-04-23 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::The partitioning of solute molecules between immiscible solvents with significantly different polarities is of great importance. The polarization between the solute and solvent molecules plays an essential role in determining the solubility of the solute, which makes computational studies utilizing molecular mechanics...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.7b00001
更新日期:2017-10-23 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::Target-oriented substructure-based virtual screening (sSBVS) of molecules is a promising approach in drug discovery. Yet, there are doubts whether sSBVS is suitable also for extrapolation, that is, for detecting molecules that are very different from those used for training. Herein, we evaluate the predictive power of...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci200472s
更新日期:2012-03-26 00:00:00
abstract::With the emergence of large collections of protein-ligand complexes complemented by binding data, as found in PDBbind or BindingMOAD, new opportunities for parametrizing and evaluating scoring functions have arisen. With huge data collections available, it becomes feasible to fit scoring functions in a QSAR style, i.e...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100264e
更新日期:2010-11-22 00:00:00
abstract::Understanding which physicochemical properties, or property distributions, are favorable for successful design and development of drugs, nutritional supplements, cosmetics, and agrochemicals is of great importance. In this study we have analyzed molecules from three distinct chemical spaces (i) approved drugs, (ii) hu...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300487z
更新日期:2013-02-25 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::Protein-polysaccharide complexes constructed via self-assembly methods are often used to develop novel biomaterials for a wide range of applications in biomedicine, food, and biotechnology. The objective of this work was to investigate theoretically and to demonstrate via constant-pH Monte Carlo simulations that the c...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.9b00814
更新日期:2020-02-24 00:00:00
abstract::The interaction between small molecules and proteins is one of the major concerns for structure-based drug design because the principles of protein-ligand interactions and molecular recognition are not thoroughly understood. Fortunately, the analysis of protein-ligand complexes in the Protein Data Bank (PDB) enables u...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci100386y
更新日期:2011-04-25 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::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::Proteins often have both orthosteric and allosteric binding sites. Endogenous ligands, such as hormones and neurotransmitters, bind to the orthosteric site, while synthetic ligands may bind to orthosteric or allosteric sites, which has become a focal point in drug discovery. Usually, such allosteric modulators bind to...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.0c00695
更新日期:2020-10-26 00:00:00
abstract::Accurate and affordable assessment of ligand-protein affinity for structure-based virtual screening (SB-VS) is a standing challenge. Hence, empirical postdocking filters making use of various types of structure-activity information may prove useful. Here, we introduce one such filter based upon three-dimensional struc...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci500319f
更新日期:2014-09-22 00:00:00
abstract::Resistance remains a major issue with regards to HIV-1 protease, despite the availability of numerous HIV-1 protease inhibitors and copious amounts of structural and binding data. In an effort to improve our understanding of how HIV-1 protease is able to "outsmart" new drugs, we have investigated the flexibility of HI...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci2000677
更新日期:2011-05-23 00:00:00
abstract::Janus kinase 2 (JAK2) is a protein tyrosine kinase implicated in signaling by specific members of the cytokine receptor family. Although it has been established that the JAK2 tyrosine kinase is negatively regulated by the JAK homology 2 (JH2) pseudokinase domain, the underlying mechanism of JH2 mediated regulation rem...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci300308g
更新日期:2012-11-26 00:00:00
abstract::The goal of the present study was to ascertain the differential performance of a long molecular dynamics trajectory versus several shorter ones starting from different points in the phase space and covering the same sampling time. For this purpose, we selected the 16-mer peptide Bak16BH3 as a model for study and carri...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/acs.jcim.6b00347
更新日期:2016-10-24 00:00:00
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...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci7003412
更新日期:2008-07-01 00:00:00
abstract::The prediction of Log P is usually accomplished using either substructure or whole-molecule approaches. However, these methods are complicated, and previous whole-molecule approaches have not been successful for the prediction of Log P in very complex molecules. The observed chemical shifts in nuclear magnetic resonan...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci049643e
更新日期:2005-03-01 00:00:00
abstract::This paper introduces the concept of an isomer network based on the reaction step counts between pairs of isomers as an alternative means to view and analyze isomer space. The computation of isomer networks is computationally expensive with respect to both run time and memory. Accordingly, this paper focuses on the de...
journal_title:Journal of chemical information and modeling
pub_type: 杂志文章
doi:10.1021/ci4005173
更新日期:2014-01-27 00:00:00