Abstract:
:The With-No-Lysine (WNK) kinase family plays a significant role in regulating cation-chloride cotransporters, blood pressure and body fluid homeostasis. Mutations in the gene of WNK family, especially in WNK1 and WNK4 are responsible for pseudohypoaldosteronism type II (PHAII), characterized by hypertension. The selective inhibition of WNK1 over other isoforms has created an immense challenge in the design of an ATP competitive inhibitor due to their high conservatism. In this work, we have compared the selectivity of the inhibitor WNK463, which was designed for WNK1 with other WNK family isoforms by comprehensive molecular modeling, docking and molecular dynamics simulations in conjunction with the Molecular Mechanics Poisson-Boltzmann Surface Area method. Our calculations show that the affinity of the inhibitor decreases in the order WNK2 > WNK1 > WNK3 > WNK4, in agreement with the experiment. Our study reveals that the inhibitor is most selective to WNK2 due to decreased polar solvation and configurational entropy compared to other isoforms. Furthermore, our analyses indicated that the nonpolar contribution from the hydrophobic residues and hydrogen bonds in the hinge region gatekeeper residue Met304 of WNK1 and its equivalent residue from other kinases played a critical role in stabilizing the inhibitor against WNK kinases. Residues Lys233, Met304, Phe356 and Leu369 of WNK1 were the essential residue differences compared to other isoforms that led to specific interactions thereby forming the basis of molecular binding pattern of binding interactions. Overall, we have identified conserved WNK-inhibitor interactions and elucidated isoform-specific interactions that could be exploited in the design of more potent and selective WNK inhibitors.Communicated by Ramaswamy H. Sarma.
journal_name
J Biomol Struct Dynjournal_title
Journal of biomolecular structure & dynamicsauthors
Jonniya NA,Kar Pdoi
10.1080/07391102.2019.1602079subject
Has Abstractpub_date
2020-03-01 00:00:00pages
1306-1321issue
5eissn
0739-1102issn
1538-0254journal_volume
38pub_type
杂志文章abstract::Histone acetyltransferases (HATs) is one among the conspicuous posttranslational modification in eukaryotic cells. p300/CBP Associated Factor (PCAF) and CREB-binding protein (CBP) are the two highly homologous HAT family which are vastly implicated in several diseases like cancer, diabetes, etc. Pentadecylidenemalonat...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1479658
更新日期:2019-06-01 00:00:00
abstract::Locked nucleic acids (LNAs) incorporated into either stable single stranded oligonucleotides containing tetraloops or their complements have been found to increase second order hybridization rate constants by an order of magnitude compared to the all-DNA hybridization rate constants. Model sequences composed of 20 bas...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2006.10507110
更新日期:2006-10-01 00:00:00
abstract::The potassium channel Kv1.3 is an important pharmacological target and the Kaliotoxin-type toxins (α-KTX-3 family) are its specific blockers. Here, we study the binding process of two kinds of Kaliotoxin-type toxins:BmKTX and its mutant (BmKTX-D33H) toward to Kv1.3 channel using MD simulation and umbrella sampling sim...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1760135
更新日期:2020-05-06 00:00:00
abstract::Target evaluation is at the centre of rational drug design and biologics development. In order to successfully engineer antibodies, T-cell receptors or small molecules it is necessary to identify and characterise potential binding or contact sites on therapeutically relevant target proteins. Currently, there are numer...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1854859
更新日期:2020-12-10 00:00:00
abstract::Cystatins are classical competitive inhibitors of C1 family cysteine proteases (papain family). Phytocystatin superfamily shares high sequence homology and typical tertiary structure with conserved glutamine-valine-glycine (Q-X-V-X-G) loop blocking the active site of C1 proteases. Here, we develop a cysteine-bounded c...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1848629
更新日期:2020-12-09 00:00:00
abstract::The effect of two widely used polyphenols, curcumin and EGCG was investigated on the amyloid fibrillogenesis of the well-characterized model protein human lysozyme (HuL), associated with non-neuropathic systemic amyloidosis, towards exploring their efficacy as modulators of HuL amyloid aggregation and toxicity and unr...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1860824
更新日期:2020-12-17 00:00:00
abstract::The amino acid sequences of the Yersinia pseudotuberculosis porin (YPS) and Y. pestis porin (YPT) have recently deduced but their three-dimensional structures were not known. These sequences were analyzed using the servers 3D-PSSM and PredPort. The YPS and YPT porins were shown to have a high degree of identity (above...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2005.10507056
更新日期:2005-10-01 00:00:00
abstract::Noonan syndrome (NS) is a common autosomal dominant congenital disorder which could cause the congenital cardiopathy and cancer predisposition. Previous studies reported that the knock-in mouse models of the mutant D61G of SHP2 exhibited the major features of NS, which demonstrated that the mutation D61G of SHP2 could...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2017.1402709
更新日期:2018-11-01 00:00:00
abstract::A series of novel carbazole based α-aminophosphonate derivatives were synthesized under solvent-free condition, characterized and evaluated for their cholinesterase inhibition, enzyme kinetic inhibition, in-vitro cell viability using N2a cells, neuroprotective studies against H2O2-induced stress using N2a cells and an...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1861981
更新日期:2020-12-21 00:00:00
abstract::This work is devoted to the careful QM/QTAIM analysis of the evolution of the basic physico-chemical parameters along the intrinsic reaction coordinate (IRC) of the biologically important 2AP·T(WC)↔2AP·T*(w) and 2AP·C*(WC)↔2AP·C(w) Watson-Crick(WC)↔wobble(w) tautomeric transformations obtained at each point of the IRC...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2017.1331864
更新日期:2018-05-01 00:00:00
abstract::Investigating the behaviour of bio-molecules through computational mutagenesis is gaining interest to facilitate the development of new therapeutic solutions for infectious diseases. The antigenetically variant genotypes of foot and mouth disease virus (FMDV) and their subsequent infections are challenging to tackle w...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1494631
更新日期:2019-07-01 00:00:00
abstract::In recent years, acetylcholinesterase (AChE) and α-glycosidase (α-gly) inhibition have emerged as a promising and important approach for pharmacological intervention in many diseases such as glaucoma, epilepsy, obesity, cancer, and Alzheimer's. In this manner, the preparation and enzyme inhibition activities of periph...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1857842
更新日期:2020-12-09 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::Ivermectin (IVM) is a broad-spectrum antiparasitic agent, having inhibitory potential against wide range of viral infections. It has also been found to hamper SARS-CoV-2 replication in vitro, and its precise mechanism of action against SARS-CoV-2 is yet to be understood. IVM is known to interact with host importin (IM...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1841028
更新日期:2020-11-02 00:00:00
abstract::The recently introduced Essential Dynamics sampling method is extended such that an exhaustive sampling of the available (backbone) configurational space can be achieved. From an initial Molecular Dynamics simulation an approximated definition of the essential subspace is obtained. This subspace is used to direct subs...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1996.10508888
更新日期:1996-04-01 00:00:00
abstract::Phospholipases A(2) (PLA(2)) are enzymes commonly found in snake venoms from Viperidae and Elaphidae families, which are major components thereof. Many plants are used in traditional medicine as active agents against various effects induced by snakebite. This article presents the PLA(2) BthTX-I structure prediction ba...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2009.10507293
更新日期:2009-08-01 00:00:00
abstract::The acute respiratory syndrome caused by the SARS-CoV-2, known as COVID-19, has been ruthlessly tormenting the world population for more than six months. However, so far no effective drug or vaccine against this plague have emerged yet, despite the huge effort in course by researchers and pharmaceutical companies worl...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1869096
更新日期:2021-01-08 00:00:00
abstract::The present study employed the spectroscopic techniques, i.e. fluorescence, and circular dichroism (CD) and the molecular docking approach to investigate the mechanism of interaction of a potent anticancer glucosinolate, sinigrin (SIN), with bovine serum albumin (BSA). SIN binding to BSA resulted in the quenching of i...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2015.1110835
更新日期:2016-10-01 00:00:00
abstract::The NIa protease of Potyviridae is the major viral protease that processes potyviral polyproteins. The NIa protease coding region of Cardamom mosaic virus (CdMV) is amplified from the viral cDNA, cloned and expressed in Escherichia coli. NIa protease forms inclusion bodies in E.coli. The inclusion bodies are solubiliz...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2012.706078
更新日期:2013-01-01 00:00:00
abstract::The aim of this study was to attempt to determine the extent to which the chemical shifts of the nonexchangeable base protons of a DNA helix depend upon the base sequence. We measured the proton NMR spectra of twelve decadeoxynucleotides in order to carry out a "statistical" treatment. In the helices, the chemical shi...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1988.10506434
更新日期:1988-02-01 00:00:00
abstract::Three-strand oligonucleotide complexes are employed to assess the effect of base stacking and base pair mismatch on the relative thermodynamic stabilities of oligonucleotide duplexes. The melting behavior of three-strand oligonucleotide complexes incorporating nicks and gaps as well as internal single base mismatches ...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2004.10506995
更新日期:2004-10-01 00:00:00
abstract::The closed loops within the proteins of the TIM-barrel fold family are analyzed and compared sequence- and structure-wise. The size distribution of the closed loops of the TIM-barrels confirms universal preference to the standard size of 25-30 residues. 3D structural RMSD comparisons of the closed loops and presentati...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2005.10507032
更新日期:2005-06-01 00:00:00
abstract::Plasma membrane of each micro-organism has a unique set of lipid composition as a consequence of the environmental adaptation or a response to exposure to antimicrobial peptides (AMPs) as antibiotic agents. Understanding the relationship between lipid composition and action of antimicrobial peptides or considering how...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2012.737295
更新日期:2013-12-01 00:00:00
abstract::Stereochemical effects of methylphosphonate (MP) in B-DNA and Z-DNA duplexes are studied through molecular mechanics approach. Duplexes of different lengths, tetramers, hexamers, dodecamers are examined to assess the interstrand and intrastrand electrostatic effects due to MPs vis-a-vis phosphates. A variety of models...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.1993.10508694
更新日期:1993-06-01 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::Changes in glycosylation pattern leads to malignant transformations among the cells. In combination with upregulated actions of sialyltransferases, it ultimately leads to differential expression of sialic acid (SA) at cell surface. Given its negative charge and localization to extracellular domain, SA has been exploit...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2018.1461690
更新日期:2019-04-01 00:00:00
abstract::The purpose of this study was to investigate the site-selective binding of erlotinib hydrochloride (ET), a targeted anticancer drug, to bovine serum albumin (BSA) through 1H NMR, spectroscopic, thermodynamic, and molecular modeling methods. The fluorescence quenching of BSA by ET was a result of the formation of BSA-E...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2012.726532
更新日期:2013-10-01 00:00:00
abstract::Novel [Pd(o-CH2C6H4P(o-tolyl)2)(histidine)] (1) and [Pd(o-CH2C6H4P(o tolyl)2)(phenylalanine)] (2) P,C-orthopalladated complexes have been prepared and characterized by elemental analysis, IR and NMR spectroscopy. To study the stability of the compounds in biological media, the complexes were incubated in Tris buffer d...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2020.1865202
更新日期:2020-12-24 00:00:00
abstract::The present paper describes design, synthesis, and biological evaluation of a series of some 3-[3-(amino)propoxy]benzenamines as acetylcholinesterase inhibitors using mice as a model and piracetam as a reference drug. The structures of these compounds were confirmed by spectral analysis and compounds were tested for m...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2016.1220330
更新日期:2017-08-01 00:00:00
abstract::Tropomyosin receptor kinase A (Trk A) is a receptor tyrosine kinase activated by nerve growth factor (NGF). TrkA plays an important role in pain sensation, which leads to significant interest in the development of small molecule inhibitors of TrkA. However, TrkA and the other two highly homologous isoforms, TrkB and T...
journal_title:Journal of biomolecular structure & dynamics
pub_type: 杂志文章
doi:10.1080/07391102.2019.1708798
更新日期:2021-01-01 00:00:00