Abstract：
:Human histone deacetylase 6 (HDAC6) has been shown to play a major role in oncogenic cell transformation via deacetylation of α-tubulin, making it a viable target of anticancer drug design and development. The crystal structure of HDAC6 catalytic domain 2 has been recently made available, providing avenues for structure-based drug design campaign. Here, in our continuous effort to identify potentially selective HDAC6 inhibitors, structure-based virtual screening of ∼72 461 compounds was carried out using Autodock Vina. The top 100 compounds with calculated ΔG < -10 kcal/mol were manually inspected for binding mode orientation. Furthermore, the top 20 compounds with reasonable binding modes were evaluated for selectivity by further docking against HDAC6 and HDAC7 using Autodock4. Four compounds with a carboxylic fragment, displayed potential selectivity for HDAC6 over HDAC7, and were found to have good druglike and ADMET properties. Their docking complexes were then submitted to 10 ns-molecular dynamics (MD) simulation using nanoscale MD (NAMD) software, to examine the stability of ligand binding modes. These predicted inhibitors remained bound to HDAC6 in the presence of water and ions, and the root-mean-square deviation (RMSD), radius of gyration (Rg) and nonbond distance (protein-ligand) profiles suggested that they might be stable over time of the simulation. This study may provide scaffolds for further lead optimization towards the design of HDAC6 inhibitors with improved selectivity.
journal_name
Comput Biol Chemjournal_title
Computational biology and chemistryauthors
Uba AI,Yelekçi Kdoi
10.1016/j.compbiolchem.2018.05.004subject
Has Abstractpub_date
2018-08-01 00:00:00pages
131-142eissn
1476-9271issn
1476-928Xpii
S1476-9271(18)30125-7journal_volume
75pub_type
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2008.02.001
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journal_title：Computational biology and chemistry
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journal_title：Computational biology and chemistry
pub_type： 杂志文章,评审
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2019.107161
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journal_title：Computational biology and chemistry
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journal_title：Computational biology and chemistry
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2015.11.006
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2004.03.001
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2007.10.003
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2008.03.020
更新日期：2008-08-01 00:00:00
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2018.04.009
更新日期：2018-08-01 00:00:00
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2018.09.010
更新日期：2018-12-01 00:00:00
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2016.09.001
更新日期：2016-10-01 00:00:00
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journal_title：Computational biology and chemistry
pub_type： 杂志文章,评审
doi：10.1016/s1476-9271(03)00050-1
更新日期：2003-12-01 00:00:00
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2017.04.006
更新日期：2017-06-01 00:00:00
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2019.04.002
更新日期：2019-06-01 00:00:00
abstract：:Previous joint experimental and theoretical work demonstrates that typically soluble peptides will be rendered insoluble in the presence of saturated sodium ions in aqueous solution due to disruption of cation-π interactions between Trp and Lys. The present work utilizes quantum chemical methods including density func...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2017.12.009
更新日期：2018-02-01 00:00:00
abstract：:Laminin-111 is a trimeric glycoprotein of the extracellular matrix (ECM) that holds a significant role in cell adhesion, migration and differentiation. Laminin-111 is the most studied laminin isoform, composed of three chains; α1, β1 and γ1. Phosphorylation is the most common eukaryotic post - translational modificati...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2018.11.021
更新日期：2019-02-01 00:00:00
abstract：:Various subsets of self-avoiding walks naturally appear when investigating existing methods designed to predict the 3D conformation of a protein of interest. Two such subsets, namely the folded and the unfoldable self-avoiding walks, are studied computationally in this article. We show that these two sets are equal an...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2013.10.001
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abstract：:Cytosine methylation is one of the most important RNA epigenetic modifications. With the development of experimental technology, scientists attach more importance to RNA cytosine methylation and find bisulfite sequencing is an effective experimental method for RNA cytosine methylation study. However, there are only a ...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2016.09.003
更新日期：2016-12-01 00:00:00
abstract：:Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disorder, and its pathogenesis in males and in cases without accompanying lupus nephritis (LN-) is not fully understood. In this study, we identified 90 (82 up- and 8 downregulated) differentially expressed genes (DEGs) common to female LN-, female LN+ a...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
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更新日期：2019-12-01 00:00:00
abstract：:In order to extract phylogenetic information from DNA sequences, the new normalized k-word average relative distance is proposed in this paper. The proposed measure was tested by discriminate analysis and phylogenetic analysis. The phylogenetic trees based on the Manhattan distance measure are reconstructed with k ran...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
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更新日期：2019-02-01 00:00:00
abstract：:Glucokinase (GK) is the main enzyme which controls the blood glucose levels in a safe and narrow physiological range in humans. GK activators are the novel type of therapeutic agents which act on GK enzyme and show their anti-diabetic potential. The present work was planned to synthesize and evaluate the antidiabetic ...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
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abstract：:A translation (framing) code based on the circular code was proposed in Michel (2012) with the identification of X circular code motifs (X motifs shortly) in the bacterial rRNA of Thermus thermophilus, in particular in the ribosome decoding center. Three classes of X motifs are now identified in the rRNAs of bacteria ...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2014.08.001
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
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journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2020.107369
更新日期：2020-12-01 00:00:00
abstract：:The human X chromosome contains a large number of inverted repeat DNA palindromes. Although arbitrary substitutions destroyed the inverted repeat structure of MAGEA/CSAG-palindrome during the evolutionary process of the primates, most of the substitutions are compensatory. Using maximum parsimony, it is demonstrated t...
journal_title：Computational biology and chemistry
pub_type： 杂志文章
doi：10.1016/j.compbiolchem.2012.11.002
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