Abstract：
:Previous work has shown that edaravone inhibits fibrillogenesis of amyloid-β protein (Aβ). However, the detailed mechanism by which edaravone inhibits the conformational transition of the Aβ42 monomer is not known at the molecular level. Here, explicit-solvent molecular dynamics (MD) simulations were coupled with molecular mechanics-Poisson-Boltzmann surface area (MM-PBSA) method to address the issue. MD simulations confirmed that edaravone inhibits the conformational transition of the Aβ42 monomer in a dose-dependent manner. It was found that the direct interactions between edaravone and Aβ42 are responsible for its inhibiting effects. The analysis of binding free energy using the MM-PBSA method demonstrated that the nonpolar interactions provide favourable contributions (about -71.7 kcal/mol). Conversely, the polar interactions are unfavourable for the binding process. A total of 14 residues were identified as greatly contributing to the binding free energy between edaravone and the Aβ42 monomer. In addition, the intra-peptide hydrophobic interactions were weakened and the salt bridge D23-K28 was interrupted by edaravone. Therefore, the conformational transition was inhibited. Our studies provide molecular-level insights into how edaravone molecules inhibit the conformational transition of the Aβ42 monomer, which may be useful for designing amyloid inhibitors.Communicated by Ramaswamy H. Sarma.
journal_name
J Biomol Struct Dynjournal_title
Journal of biomolecular structure & dynamicsauthors
Liu F,Ma Z,Sang J,Lu Fdoi
10.1080/07391102.2019.1632225subject
Has Abstractpub_date
2020-05-01 00:00:00pages
2377-2388issue
8eissn
0739-1102issn
1538-0254journal_volume
38pub_type
杂志文章abstract：:Our earlier study on the nucleosomes containing TBP binding sites (TATA boxes) indicated that generally the same sequence, which harbors the TATA box, encodes simultaneously an alternative rotational setting of the box, so that the TATA element is either exposed (position "minor groove out") or hidden in position "min...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2015.1134348
更新日期：2016-12-01 00:00:00
abstract：:It is well known that the biological activity of gallated proanthocyanidins (PAs) is highly structure-dependent. Polymerization degree (DP) and linkage types affect their biological activity greatly. Positions and orientations of gallated PAs in lipid bilayer reveal their structure-function activity at the molecular l...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2017.1369163
更新日期：2018-08-01 00:00:00
abstract：:Interaction between a cationic porphyrin and its ferric derivative with oligo(dA.dT)15 and oligo(dG.dC)15 was studied by UV-vis spectroscopy, resonance light scattering (RLS), and circular dichroism (CD) at different ionic strengths; molecular docking and molecular dynamics simulation were also used for completion. Fo...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2014.963674
更新日期：2015-01-01 00:00:00
abstract：:Pertussis, caused by Bordetella pertussis is still one of the controversial diseases worldwide due to its high prevalence in both the developed and the developing countries, especially among young children. As currently approved vaccines are not protective enough and provide Th2-type immune responses, there is an urge...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2020.1794966
更新日期：2020-07-21 00:00:00
abstract：:Short and long disordered regions of proteins have different preference for different amino acid residues. Different methods often have to be trained to predict them separately. In this study, we developed a single neural-network-based technique called SPINE-D that makes a three-state prediction first (ordered residue...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/073911012010525022
更新日期：2012-01-01 00:00:00
abstract：:About one-third of the existing proteins require metal ions as cofactors for their catalytic activities and structural complexities. While many of them bind only to a specific metal, others bind to multiple (different) metal ions. However, the exact mechanism of their metal preference has not been deduced to clarity. ...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2015.1080629
更新日期：2016-07-01 00:00:00
abstract：:1, 4 and 5, 8-Positions as well as type of functionalities on these positions at anthraquinone-9, 10-dione are proposed to be significant for anticancer activity. Therefore, keeping this into consideration, a series of 1-substituted anthraquinone-based compounds are designed, synthesized, characterized and biologicall...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2018.1552198
更新日期：2019-10-01 00:00:00
abstract：:Linezolid, one of the reserve antibiotic of oxazolidinone class has wide range of antimicrobial activity. Here we have conducted a fundamental study concerning the dynamics of its interaction with bovine serum albumin (BSA), and the post binding modification of the later by employing different spectroscopic (absorptio...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2017.1278721
更新日期：2018-02-01 00:00:00
abstract：:Understanding, at the molecular level, the effect of AMPs on biological membranes is of crucial importance given the increasing number of multidrug-resistant bacteria. Being part of an ancient type of innate immunity system, AMPs have emerged as a potential solution for which bacteria have not developed resistance. Tr...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2020.1867640
更新日期：2021-01-05 00:00:00
abstract：:Self-association of α-synuclein (αS) into pathogenic oligomeric species and subsequent formation of highly ordered amyloid fibrils is linked to the Parkinson's disease. So most of the recent studies are now focused on the development of potential therapeutic strategies against this debilitating disease. β-synuclein (β...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2016.1254119
更新日期：2017-11-01 00:00:00
abstract：:Human male germ cell-associated kinase (hMAK) is an androgen-inducible gene in prostate epithelial cells, and it acts as a coactivator of androgen receptor signaling in prostate cancer. The 3D structure of the hMAK kinase was modeled based on the crystal structure of CDK2 kinase using comparative modeling methods, and...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2014.968622
更新日期：2015-01-01 00:00:00
abstract：:The EPR study of spin labeled macromolecules has provided insight into structural and dynamical properties of DNA, proteins, and related systems. While spin labeling has been useful, it is experimentally difficult to determine if the spin label significantly alters the conformation of the macromolecule to which it is ...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2005.10507028
更新日期：2005-04-01 00:00:00
abstract：:The empirical potential including the intra- and intermolecular energy terms was used to study the interaction of L-Lysine-L-Alanine-L-Alanine Tripeptide with four models of B-DNA with different compositions. On the basis of a detailed search of the respective potential energy surface, it was found that the peptide is...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.1994.10508038
更新日期：1994-02-01 00:00:00
abstract：:We study the CaM-peptide interactions for four CaM-related peptides with different calcium equivalents, using the hCaM-M124C-mBBr biosensor and Molecular Dynamics (MD). Due to the high sensitivity of the biosensor, we were able to calculate five Kds based on the number of calcium equivalents for each peptide, showing ...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2020.1841679
更新日期：2020-10-30 00:00:00
abstract：:Aminoacyl tRNA synthetases are enzymes that specifically attach amino acids to cognate tRNAs for use in the ribosomal stage of translation. For many aminoacyl tRNA synthetases, the required level of amino acid specificity is achieved either by specific hydrolysis of misactivated aminoacyl-adenylate intermediate (pre-t...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2016.1155171
更新日期：2017-02-01 00:00:00
abstract：:The object of the present study is the verification of a new approach to the design of the active truncated forms of enzymes. The method is based on a new way of investigating the protein sequences--the ANalysis of Informational Structure (ANIS). The analysis of informational structure allows to determine the hierarch...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2007.10507133
更新日期：2007-04-01 00:00:00
abstract：:The development of SrtA inhibitors targeting the biothreat organism namely Bacillus anthracis was achieved by the combined approach of pharmacophore modeling, binding interactions, electron transferring capacity, ADME, and Molecular dynamics studies. In this study, experimentally reported Ba-SrtA inhibitors (pyridazin...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2013.818577
更新日期：2014-01-01 00:00:00
abstract：:Monte-Carlo simulation of poly(dA).poly(dT) hydration by 30 water molecules per nucleotide pair has been performed. Two B-family conformations, both with a 36 degrees helical twist but with different minor groove widths, were considered. One conformation is Arnott's standard B form, the other one is specific for poly(...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.1988.10506508
更新日期：1988-12-01 00:00:00
abstract：:Tau-tubulin kinase 1 inhibitors inhibit tau protein phosphorylation on Ser198, Ser199, Ser202, Ser422, and also in paired helical filaments. We developed receptor-based pharmacophore models by exploiting three TTBK1 protein structures, i.e., 4NFN, 4BTM, and 4BTK. The integrated e-pharmacophore based virtual screening ...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2019.1590242
更新日期：2020-02-01 00:00:00
abstract：:P21-activated kinase 4 (PAK4) is a serine/threonine protein kinase, which is associated with many cancer diseases, and thus being considered as a potential drug target. In this study, three-dimensional quantitative structure-activity relationship (3D-QSAR), molecular docking and molecular dynamics (MD) simulations wer...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2019.1673823
更新日期：2020-09-01 00:00:00
abstract：:Preceding experimental findings revealed that the release of indomethacin decreased when a folate conjugate G4-PAMAM (folate-G4-PAMAM) dendrimer was used compared with its unconjugated dendrimer (G4-PAMAM). Further, better encapsulation of the conjugated dendrimer was achieved, information useful for elucidating the s...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2020.1861984
更新日期：2020-12-21 00:00:00
abstract：:We studied the Tetrahymena thermophila rRNA IVS sequence with the aim of obtaining a model of the structure characterized by the bases proximity of the self-reactions sites. The considered sequence kept up those fragments essential for its catalytic activity as demonstrated by deletion mutants. The first step was the ...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.1991.10507864
更新日期：1991-04-01 00:00:00
abstract：:A conceptually new idea in quantitative structure-activity relationships (QSAR) which makes use of ensembles from molecular dynamics (MD) trajectories and information retrieved from enzyme-inhibitor binding thermodynamics is presented in this study. This new methodology, termed ensemble comparative residue interaction...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2014.909744
更新日期：2015-01-01 00:00:00
abstract：:Transient interactions between cancer stem cells and components of the tumor microenvironment initiate various signaling pathways crucial for carcinogenesis. Predominant hyaluronan (HA) receptor, CD44 is structurally and functionally one of the most variable cell surface receptors having the potential to generate a di...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2016.1142476
更新日期：2017-02-01 00:00:00
abstract：:Our work investigates the interaction of synthesized graphene with the SARS-CoV-2 virus using molecular docking and molecular dynamics (MD) simulation method. The layer dependent inhibitory effect of graphene nanosheets on spike receptor-binding domain of 6LZG, complexed with host receptor i.e. angiotensin-converting ...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2020.1817788
更新日期：2020-09-11 00:00:00
abstract：:Rho-associated protein kinases (ROCKs) are a member of the serine/threonine protein kinase family and potential therapeutic target for various diseases. This enzyme has two isoforms, Rho-associated protein kinase I (ROCKI) and Rho-associated protein kinase II (ROCKII). They share an overall 65% homology in all amino a...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2018.1491420
更新日期：2019-06-01 00:00:00
abstract：:Abstract Using high frequency antiphase NMR spectroscopy and computer simulations of the antiphase spectra, we studied the equlibria in the sugar conformations in the DNA duplex 11-mer containing the AAA tract surrounded by cytosines. We demonstrate that at the 3'-end of the A-tract, the sugar switches from the comm...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2000.10506637
更新日期：2000-01-01 00:00:00
abstract：:Enumerating procedure for symbol sequences is proposed. Relationship between Hamming distance for symbol sequences and Euclidean distance for corresponding enumerations is established, and more universal Hamming-transformed Euclidean measure is constructed. A distribution function of amino acid substitutions and some ...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.1997.10508187
更新日期：1997-10-01 00:00:00
abstract：:Enzymes involved in the pyrimidine biosynthesis pathway have become an important target for the pharmacological intervention. One among those enzymes, Aspartate Trans Carbamoylase (ATCase), catalyses the condensation of aspartate and carbamoyl phosphate to form N-carbamoyl-l-aspartate and inorganic phosphate. The pres...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2013.782825
更新日期：2014-04-01 00:00:00
abstract：:SARS-CoV-2 cause fatal infection in 213 countries accounting for the death of millions of people globally. In the present study, phytochemicals from spices were assessed for their ability to interact with SARS-CoV-2 MPro. Structure based virtual screening was performed with 146 phytochemicals from spices using Autodoc...
journal_title：Journal of biomolecular structure & dynamics
pub_type： 杂志文章
doi：10.1080/07391102.2020.1845980
更新日期：2020-11-17 00:00:00
