Abstract：
:Cathepsin S has been demonstrated to play a crucial role in the remodeling of extracellular matrix proteins such as elastin and collagen, which in turn contribute to the structural integrity of the cardiovascular wall. Atherosclerotic lesions, aneurysm formation, plaque rupture, thrombosis, and calcification are some of the cardiovascular disorders related to cathepsin S. A highly selective inhibitor of human as well as animal cathepsin S, RO5444101, was recently reported to attenuate the progression of atherosclerotic lesions. Here, we attempted to gain insight into the molecular mechanism of action of RO5444101 on cathepsin S by performing molecular docking and molecular dynamics (MD) simulation studies. The results of our studies correlate well with relevant reported experimental data and potentially explain the selectivity of this inhibitor for cathepsin S rather than cathepsin L1/L, cathepsin L2/V, and cathepsin K, which share conserved catalytic sites and have sequence similarities of 49%, 50%, and 55%, respectively, with respect to cathepsin S. In contrast to those closely related cathepsins, 20 ns MD simulation data reveal that the overall interaction of cathepsin S with RO5444101 is more stable and involves more protein-molecule interactions than the interactions of the inhibitor with the other cathepsins. This study therefore considerably improves our understanding of the molecular mechanism responsible for cathepsin S inhibition and facilitates the identification of potential novel selective inhibitors of cathepsin S.
journal_name
J Mol Modeljournal_title
Journal of molecular modelingauthors
Ahmad S,Siddiqi MIdoi
10.1007/s00894-017-3255-6subject
Has Abstractpub_date
2017-03-01 00:00:00pages
92issue
3eissn
1610-2940issn
0948-5023pii
10.1007/s00894-017-3255-6journal_volume
23pub_type
杂志文章abstract：:Fine-tuning of magnetic states via an understanding of spin injection on the edge of graphene nanoribbons should allow for greater flexibility of the design of graphene-based spintronics. On the basis of calculations, we predict that coupling constants of the exchange interaction in the series of nitroxide-functionali...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-3944-4
更新日期：2019-02-09 00:00:00
abstract：:Through the B3LYP/6-311++G(d,p) calculations, theoretical studies of structural parameters, electronic properties, infrared vibration modes, and charge density topologies on the C2H4O∙∙∙HX and C2H5N∙∙∙HX (X = F or O-F) heterocylic hydrogen complexes are presented. The H-bond distances and high energies point out stron...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-015-2829-4
更新日期：2015-11-01 00:00:00
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pub_type： 杂志文章
doi：10.1007/s00894-005-0064-0
更新日期：2006-03-01 00:00:00
abstract：:Checkpoint kinase 1 (Chk1), a member of the serine/threonine kinase family, is an attractive therapeutic target for anticancer combination therapy. A structure-based modeling approach complemented with shape components was pursued to develop a reliable pharmacophore model for ATP-competitive Chk1 inhibitors. Common ch...
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pub_type： 杂志文章
doi：10.1007/s00894-009-0630-y
更新日期：2010-07-01 00:00:00
abstract：:Recently inulinase has regained interest due to its usage in the production of fructooligosaccharides, biofuels, and in pharmaceutical industries. Inulinases properties are experimentally reported by nomerous studies but their characteristics are just partially explained by only a few computational investigations. In ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-016-2935-y
更新日期：2016-04-01 00:00:00
abstract：:Very recently, an unprecedented novel monometallic cluster of fullerenes entrapping a yttrium cyanide (YCN) cluster inside a popular C82 cage YCN@Cs(6)-C82 was synthesized and characterized. Inspired by this investigation, four non-IPR YCN@C1(17459)-C76, YCN@C2v(19138)-C76, YCN@C2(17646)-C76, and YCN@C1(17894)-C76 (1,...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-016-3040-y
更新日期：2016-08-01 00:00:00
abstract：:The present study reports the geometry, electronic structure and properties of neutral and anionic transition metal (TM = Ti, Zr and Hf)) doped germanium clusters containing 1 to 20 germanium atoms within the framework of linear combination of atomic orbitals density functional theory under spin polarized generalized ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-011-1122-4
更新日期：2012-01-01 00:00:00
abstract：:Ten functionals were used to assess their capability to compute a local reactivity descriptor coming from the Conceptual Density Functional Theory on a group of iron-based organometallic compounds that have been synthesized by Zohuri, G.H. et al. in 2010; these compounds bear the following substituent groups: H-, O2N-...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3576-5
更新日期：2018-01-18 00:00:00
abstract：:We report a DFT, TDDFT and DFTB investigation of the performance of two donor-π-acceptor (D-π-A)-type organic dyes bearing different electron-withdrawing groups (EWG) for dye-sensitized solar cells (DSSCs) to evaluate which EWG is better for an acrylic acid acceptor, i.e., Cyano (-CN) or o-nitrophenyl (o-NO2-Ph). A se...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-012-1719-2
更新日期：2013-04-01 00:00:00
abstract：:The reaction mechanism of Ru-catalyzed cycloisomerization of 2-alkynylanilides to 3-substituted indole or 2-substituted indole was analyzed at the B3LYP level of density functional theory. The solvation effect of the system was also considered by SMD model. The calculation results show that the reaction system first f...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-018-3707-7
更新日期：2018-06-14 00:00:00
abstract：:Nowadays, scientists are trying to develop low-cost fullerene free acceptors for small organic photovoltaic cells in order to overcome the limitations of fullerene derivatives. Current research work deals with theoretical study on three non-fullerene acceptors based on indaceno, dithiophene core, and thiophene bridge ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-4198-x
更新日期：2019-09-11 00:00:00
abstract：:In this work, the spectroscopic information, stability and aromaticity of the boron-nitrogen azulene and naphthalene molecules are provided by the use of CC2 (geometry optimization, dipole moment, UV-vis spectrum calculations) and DFT (vibrational spectrum and NMR calculations) methodologies. One isomer of the investi...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3279-y
更新日期：2017-04-01 00:00:00
abstract：:The geometrical parameters and static electric properties of several metal porphyrin halides, including Fe(III) porphine chloride (FePCl), Fe(III) porphine bromide (FePBr), Fe(III) tetraphenylporphine chloride (FeTPPCl), aluminum phthalocyanine chloride (AlPcCl), gallium(III) phthalocyanine chloride (GaPcCl), and mang...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-009-0556-4
更新日期：2010-03-01 00:00:00
abstract：:Isothiocyanates (ITC) are well-known chemopreventive agents extracted from vegetables. This activity results from the activation of human oxidoreductase. In this letter, the uncompetitive activatory mechanism of ITC was investigated using docking and molecular dynamics simulations. This indicates that NAD(P)H:quinone ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-009-0628-5
更新日期：2010-07-01 00:00:00
abstract：:An azo bridge (-N=N-) can not only desensitize explosives but also dramatically increase their heats of formation and explosive properties. Amino and nitro are two important high energy density functional groups. Here, we present calculations on 1-nitro-1-triazene (NH2-N=N-NO2). Thermal stability and detonation parame...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-014-2362-x
更新日期：2014-08-01 00:00:00
abstract：:Adsorption of three heavy metals (Ni, Pd, Cd) onto (10,0) single-walled carbon nanotube (SWCNT) was investigated using density functional theory (DFT). Metals were adsorbed to both inside and outside of SWCNT and their structures and electronic properties [e.g., band structures and density of states (DOS)] were calcul...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-4062-z
更新日期：2019-06-10 00:00:00
abstract：:The mechanism of the copper(I)-catalyzed cyclopropanation reaction for methyl diazoacetate with both (Z)- and (E)-but-2-ene stereoisomers has been studied using the 6-311++G(d,p) basis set by means of M06-2X and O3LYP functionals. According to both methods, the rate-limiting step is the formation of a copper-carbene i...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-018-3737-1
更新日期：2018-07-05 00:00:00
abstract：:We report results of numerical simulations of complex fluids, using a combination of discrete-particle methods. Our molecular modeling repertoire comprises three simulation techniques: molecular dynamics (MD), dissipative particle dynamics (DPD), and the fluid particle model (FPM). This type of model can depict multi-...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-001-0068-3
更新日期：2002-01-01 00:00:00
abstract：:Defects in the nanoscale are common in the 2D materials irrespective of the fabricated method. Material performance gets significantly affected due to the presence of defects in 2D materials. In the present study, electronic and mechanical properties of 2D-hexagonal boron nitride (hBN) are investigated. At the electro...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-020-04452-y
更新日期：2020-07-03 00:00:00
abstract：:CD44 is a cell-surface glycoprotein and receptor for hyaluronan, one of the major components of the tumor extracellular matrix. There is evidence that the interaction between CD44 and hyaluronan promotes breast cancer metastasis. Recently, the molecule F-19848A was shown to inhibit hyaluronan binding to receptor CD44 ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-016-3029-6
更新日期：2016-07-01 00:00:00
abstract：:Iridium (III) 2-phenylpyridine (ppy) complexes with two suitable monodentate L ligands [Ir(ppy)₂(L)₂]⁺ (ppy = 2-phenylpyridine, py = pyridine, L = 4-pyCN 1, 4-pyCHO 2, 4-pyCl 3, py 4, 4-pyNH₂ 5) were studied by density functional theory (DFT) and time-dependent DFT methods. The influences of ligands L on the electroni...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-012-1462-8
更新日期：2012-10-01 00:00:00
abstract：:Epidermal growth factor receptors (EGFR) are associated with a number of biological processes and are becoming increasingly recognized as important therapeutic targets against cancer. In this work, we provide models based on homology for the extracellular domains (ECD) of ErbB3 and ErbB4 in their active conformations,...
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pub_type： 杂志文章
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更新日期：2013-02-01 00:00:00
abstract：:Various kinetic studies of the addition of hydrogen halides to alkenes were carried out in the 1930s, 1940s, and 1970s. Since then, there have been theoretical analyses of several aspects of alkene reactivity and regioselectivity during hydrohalogenation. A few works have studied the influence of the hydrogen halide w...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-4004-9
更新日期：2019-04-25 00:00:00
abstract：:In erythrocytes, actively multiplying Plasmodium falciparum parasites exhibit a unique signature of virulence associated histone modifications, thereby epigenetically regulating the expression of the majority of genes. Histone acetylation is one such modification, effectuated and maintained by the dynamic interplay of...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-018-3761-1
更新日期：2018-08-14 00:00:00
abstract：:The mechanism and origin of selectivity for [3 + 2]-cycloaddition (32CA) reactions between thioketone and carbohydrate-derived nitrones in THF were investigated by using the density functional theory (DFT) at the M06-2X/6-311+G(d,p)//M06-2X/6-31+G(d,p) level of theory combined with the solvation SMD model. The calcula...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-4104-6
更新日期：2019-07-02 00:00:00
abstract：:In quantum chemical calculations, there are two facts of particular relevance: the position-dependent mass Schrödinger equation (PDMSE) and the exponential-type potentials used in the theoretical study of vibrational properties for diatomic molecules. Accordingly, in this work, the treatment of exactly solvable PDMSE ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-4159-4
更新日期：2019-08-31 00:00:00
abstract：:The USFDA has approved pramlintide, commercially named Symlin (sIAPP), as adjunctive therapy for type 2 diabetes (T2D). This analogue of the human amylin peptide (hIAPP) has triple proline substitutions typical of the rat isoform (rIAPP). Recently, it was proposed that pramlintide solubility and aggregation resistance...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-4137-x
更新日期：2019-08-19 00:00:00
abstract：:Ab initio computations are performed to study the structural, elastic, electronic, and vibrational characteristics of the cubic antiperovskite compound PbNCa3 under pressure up to 50 GPa. By using the generalized gradient approximation (GGA), the equilibrium structural parameters, energy band structure, density of sta...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-020-04656-2
更新日期：2021-01-03 00:00:00
abstract：:In this work, the poly(ethylene oxide) bulk as one example has been iteratively heated and cooled back using MD simulations to examine the effects of thermal history on the resulting Tg. It is demonstrated that, after the system is equilibrated once at the high temperatures, the simulated Tg does not exhibit a systema...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3439-0
更新日期：2017-08-22 00:00:00
abstract：:The drug discovery process typically involves target identification and design of suitable drug molecules against these targets. Despite decades of experimental investigations in the drug discovery domain, about 96% overall failure rate has been recorded in drug development due to the "undruggability" of various ident...
journal_title：Journal of molecular modeling
pub_type： 杂志文章,评审
doi：10.1007/s00894-020-04385-6
更新日期：2020-05-08 00:00:00
