Abstract：
:A good understanding of the inhibition mechanism of enzymes exhibiting high levels of similarity is the first step to the discovery of new drugs with selective potential. Examples of such proteins include glycogen synthase kinase-3 (GSK-3β) and cyclin-dependent kinase 2 (CDK-2). This article reports the mechanism of such enzyme inhibition as analyzed by an indoline sulfamylophenyl derivative (CHEMBL410072). Previous work has shown that such compounds exhibit selective properties towards their biological targets. This study used a combined procedure involving docking and molecular dynamics simulations, which allowed identification of interactions responsible for stabilization of complexes, and analysis of the dynamic stability of the systems obtained. The initial data obtained during the molecular docking stage show that the ligand molecule exhibits a similar affinity towards both active sites, which was confirmed by quantification of identified interactions and energy values. However, the data do not cover dynamic aspects of the considered systems. Molecular dynamics simulations realized for both complexes indicate significant dissimilarities in dynamics properties of both side chains of the considered ligands, especially in the case of the part containing the sulfamide group. Such increased mobility of the analyzed systems disrupts the stability of binding in the stabilized complex with GSK-3β protein, which finally affects also the binding affinity of the ligand molecule towards this enzyme.
journal_name
J Mol Modeljournal_title
Journal of molecular modelingauthors
Czeleń Pdoi
10.1007/s00894-017-3395-8subject
Has Abstractpub_date
2017-08-01 00:00:00pages
230issue
8eissn
1610-2940issn
0948-5023pii
10.1007/s00894-017-3395-8journal_volume
23pub_type
杂志文章abstract：:The unsaturated trinuclear iron fluoroborylene complexes Fe3(BF)3(CO) n (n = 7, 6) have been studied using density functional theory (DFT). Relatively complicated potential energy surfaces are found with nine and eight structures within 15 kcal mol-1 of the lowest energy structures for the Fe3(BF)3(CO)7 and Fe3(BF)3(C...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3301-4
更新日期：2017-04-01 00:00:00
abstract：:4-hydroxybenzoate oligoprenyltransferase of E. coli, encoded in the gene ubiA, is an important key enzyme in the biosynthetic pathway to ubiquinone. It catalyzes the prenylation of 4-hydroxybenzoic acid in position 3 using an oligoprenyl diphosphate as a second substrate. Up to now, no X-ray structure of this oligopre...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-004-0197-6
更新日期：2004-12-01 00:00:00
abstract：:The effects of L-serine amino acid functionalization on a graphene plane were investigated through density functional theory calculations compared with those of oxygen functionalization. Three systems of 4 × 4 graphene supercells were created and functionalized by an epoxy group, a hydroxyl group, and an L-serine mole...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-020-04466-6
更新日期：2020-07-13 00:00:00
abstract：:We use density functional theory-based calculations to study structural, electronic, and magnetic properties of two key reaction intermediates on a hematite, [Formula: see text]-Fe2O3, photoanode during the solar-driven water splitting reaction. Both intermediates contain an oxygen atom bonded to a surface iron atom. ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-018-3815-4
更新日期：2018-09-18 00:00:00
abstract：:Nitrogen (N)-doped carbons reportedly exhibit good electrocatalytic activity for the oxygen reduction reaction (ORR) of fuel cells. This work provides theoretical insights into the ORR mechanism of N-doped graphene by using density functional theory calculations. All possible reaction pathways were investigated, and t...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-013-2047-x
更新日期：2013-12-01 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：:Hydrogenoxalate (charge -1) and oxalate (charge -2) anions and their solvated forms were studied by various computational techniques. Ab initio quantum chemical calculations in gas phase, in implicit solvent and microsolvated (up to 32 water molecules) environment were performed in order to explore a potential energy ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-016-3075-0
更新日期：2016-09-01 00:00:00
abstract：:G-Quadruplex and i-Motif-forming sequences in the promoter regions of several oncogenes show promise as targets for the regulation of oncogenes. In this study, molecular models were created for the c-MYC NHE-III(1) (nuclease hypersensitivity element III(1)) from two 39-base complementary sequences. The NHE modeled her...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-007-0254-z
更新日期：2008-02-01 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：:Abnormal expression of cyclin-dependent kinase 2 (CDK2)/cyclin-E is detected in colorectal, ovarian, breast and prostate cancers. The study of CDK2 with a bound inhibitor revealed CDK2 as a potential therapeutic target for several proliferative diseases. Several highly selective inhibitors of CDK2 are currently underg...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-012-1620-z
更新日期：2013-02-01 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：:We present a theoretical study of the adsorption of 2,2,6,6-tetramethylpiperidine-1-oxoammonium cation (TEMPO) onto the TiO₂(110) surface rutile, investigating its bonding nature, electron properties and structural stability. Based on the results obtained with the PBE0/def2-SVP method, natural bond orbital (NBO) analy...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-014-2149-0
更新日期：2014-03-01 00:00:00
abstract：:Cystic fibrosis (CF), the most common lethal genetic disease among Caucasians, is caused by mutations in cystic fibrosis transmembrane conductance regulator (CFTR). CFTR's main role is to transport chloride ions across epithelial cell membranes. It also regulates many cell functions. However, the exact role of CFTR in...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-011-1029-0
更新日期：2012-01-01 00:00:00
abstract：:The structures, energetics, as well as several important chemical parameters, of antiretroviral drugs - nucleoside reverse transcriptase inhibitors (NRTIs) - and natural deoxyribonucleosides in both neutral, and positively and negatively charged states, are investigated. These studies are carried out within the frame ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-012-1391-6
更新日期：2012-08-01 00:00:00
abstract：:Conjugate peak refinement (CPR) is a powerful and robust method to search transition states on a molecular potential energy surface. Nevertheless, the method was to the best of our knowledge so far only implemented in CHARMM. In this paper, we present PyCPR, a new Python-based implementation of the CPR algorithm withi...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-016-3116-8
更新日期：2016-10-01 00:00:00
abstract：:Ab initio calculations have been performed using the complete basis set model (CBS-QB3) to study the reaction mechanism of butane radical (C(4)H(9)•) with oxygen (O(2)). On the calculated potential energy surface, the addition of O(2) to C(4)H(9)• forms three intermediates barrierlessly, which can undergo subsequent i...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-011-1241-y
更新日期：2012-05-01 00:00:00
abstract：:Colorectal cancer, which is considered one of the leading causes of mortality worldwide, develops through the formation of benign polyps on the inner colon or rectum wall. Truncations in adenomatous polyposis coli (APC) gene lead to the spread of the disease in the entire colon region when combined with the guanine nu...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-020-04467-5
更新日期：2020-07-16 00:00:00
abstract：:PB1-F2 is a recently described influenza A viral protein that induces apoptosis by binding with two mitochondrial membrane proteins, i.e. VDAC1 (outer membrane) and ANT3 (inner membrane). Knowledge of this binding mechanism could provide insights that would aid in the design of novel inhibitors against this protein. T...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-009-0555-5
更新日期：2010-03-01 00:00:00
abstract：:The present study deals with the decomposition of CF(3)OCF(2)O radical formed from a hydrofluoroether, CF(3)OCHF(2) (HFE-125), in the atmosphere. The study is performed using ab initio quantum mechanical methods. Two plausible pathways of decomposition of the titled species have been considered, one involving C-O bond...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-010-0735-3
更新日期：2011-03-01 00:00:00
abstract：:The theoretical three-dimensional structure of a novel δ-endotoxin Cry1Id (81 kDa) belonging to Cry1I class, toxic to many of the lepidopteran pests has been investigated through comparative modeling. Molecular dynamics (MD) simulations was carried out to characterize its structural and dynamical features at 10 ns in ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
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更新日期：2013-12-01 00:00:00
abstract：:In this study, the binding of Bovine serum albumin (BSA) with three flavonoids, kaempferol-3-O-a-L-rhamnopyranosyl-(1-3)-a-L-rhamnopyranosyl-(1-6)-b-D-galacto- pyranoside (drug 1),kaempfol-7-O-rhamnosyl-3-O-rutinoside (drug 2)andkaempferide-7-O-(4"-O-acetylrhamnosyl)-3-O-ruti- noside (drug 3) is investigated by molecu...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
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更新日期：2013-03-01 00:00:00
abstract：:Hepatic fibrosis is a common complication of the infection by the parasite, Clonorchis sinensis. There is a high incidence of this disease in the Asian countries with an increased risk of conversion to cancer. A secretory phospholipase A(2) (PLA(2)) enzyme from the parasite is implicated in the pathology. This is an a...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-011-1333-8
更新日期：2012-07-01 00:00:00
abstract：:Hydrogen dissociative chemisorption and desorption on small lowest energy Ni(n) clusters up to n=13 as a function of H coverage was studied using density functional theory. H adsorption on the clusters was found to be preferentially at edge sites followed by 3-fold hollow sites and on-top sites. The minimum energy pat...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-011-1059-7
更新日期：2011-09-01 00:00:00
abstract：:A practical mixed basis set was developed to facilitate accurate calculations of potential energy surfaces for π-stacking interactions. Correlation consistent basis sets (cc-PVXZ) were augmented by p-type Gaussian functions placed above and below the planes of C6 moieties. Møller-Plesset (MP2, SCS-MP2) and coupled clu...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-014-2558-0
更新日期：2015-01-01 00:00:00
abstract：:Amorphous molecular simulation to model the reaction species in the synthesis of chemically inert and energetic 1,1-diamino-2,2-dinitroethene (DADNE) explosive material was performed in this work. Nitromethane was selected as the starting reactant to undergo halogenation, nitration, deprotonation, intermolecular conde...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-016-3182-y
更新日期：2017-01-01 00:00:00
abstract：:Recently, the massively parallel computation of absolute binding free energy with a well-equilibrated system (MP-CAFEE) has been developed. The present study aimed to determine whether the MP-CAFEE method is useful for drug discovery research. In the drug discovery process, it is important for computational chemists t...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-010-0728-2
更新日期：2011-02-01 00:00:00
abstract：:We studied the structure and dynamics of star-shaped polymers by means of coarse-grained molecular dynamics simulations and analysis of structural transitions of semi-flexible macromolecules confined in nano-channels. The conformation of star arms in narrow channels is given by the channel width, arm flexibility and n...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-015-2735-9
更新日期：2015-07-01 00:00:00
abstract：:A detailed investigation of the structure, electronic, spectroscopic, and optical properties of a series of transition metal-doped tetraphenylporphyrins (TM-TPP; TM = Fe, Co, Ni, Cu and Zn) is performed under density functional framework. The structure and stability of tetraphenylporphyrin (TPP) and TM-TPPs are unders...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-018-3783-8
更新日期：2018-08-18 00:00:00
abstract：:A survey of the fascinating history of anesthetics and the many critical findings that have improved our understanding of anesthetic activity is followed by an expanded analysis of the electrostatic potentials of 27 molecules and two noble gases with anesthetic activities ranging from high to totally inactive. We agai...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3547-x
更新日期：2017-12-19 00:00:00
abstract：:Using density functional theory (DFT) and molecular dynamics (MD), we studied the interaction of a titanium atom with a half of a C60 fullerene (i.e., C30), formed from the corannulene structure with a pentagonal base. We considered atmospheric pressure and 300 K. We found that the most stable adsorption of the titani...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-016-3086-x
更新日期：2016-09-01 00:00:00
