Abstract：
:3-phosphoinositide-dependent protein kinase-1 (PDK1) plays a crucial role in the signal transduction of massive growth-related protein kinases. In this work, a computational study has been performed to investigate the binding pose of the hydrolyzed product of SBF1 (SBF1-) with PDK1. The binding pose was predicted by Vina and was further refined in a molecular dynamics simulation. For comparison, four published low molecular weight compounds (PS48, PS171, PS182, and PS210) binding with PDK1 were also studied. SBF1- was anchored in the PIF-pocket of PDK1 with salt bridge interaction using its carboxylate moiety, which is a common feature among the known ligands. Hydrogen bonds to THR148 and vdW interactions with GLN150 also have contributions to the association affinity. The allosteric regulation on PDK1 via the binding of SBF1- was further addressed. The binding affinity of SBF1- in complex with PDK1 is comparable to those of PS171 and PS182, with an estimated IC50 in a range from 2.0 to 10.0 μ molar. Comparison between the free energy profiles with the presence or absence of SBF1- in the binding pocket indicates that the binding of SBF1- enhances the hinge motion and suppresses the fluctuation of the end-to-end distance in α B of PDK1. These results demonstrate that SBF1- is a promising allosteric regulator of PDK1 targeting the PIF-binding pocket and can serve as a new scaffold template for the design of new drugs targeting PDK1.
journal_name
J Mol Modeljournal_title
Journal of molecular modelingauthors
Liu W,Li P,Mei Ydoi
10.1007/s00894-019-4069-5subject
Has Abstractpub_date
2019-06-13 00:00:00pages
187issue
7eissn
1610-2940issn
0948-5023pii
10.1007/s00894-019-4069-5journal_volume
25pub_type
杂志文章abstract：:The original version of this article unfortunately contained a mistake. Schemes I and II were missing. These important components are given below. ...
journal_title：Journal of molecular modeling
pub_type： 已发布勘误
doi：10.1007/s00894-017-3466-x
更新日期：2017-11-01 00:00:00
abstract：:Mechanical properties of graphene- and carbon nanotube-reinforced Araldite LY 5052/Aradur HY 5052 epoxy resins were investigated by molecular dynamics simulations. The COMPASS II force field was implemented in the simulations. Mechanical properties of the reinforced araldite/aradur resin epoxy system with CNT reveal t...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-4085-5
更新日期：2019-06-15 00:00:00
abstract：:Remarkable advances have been made in the drug therapy of tuberculosis. However much remains to be learned about the molecular and structural basis of drug resistance in Mycobacterium tuberculosis. It is known that, activation of Isoniazid (INH) is mediated by Mycobacterium tuberculosis catalase-peroxidase (MtBKatG) a...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-010-0785-6
更新日期：2011-04-01 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：:This paper used numerical and experimental methods to investigate the mechanical properties of amorphous NiAl alloys during the nanoindentation process. A simulation was performed using the many-body tight-binding potential method. Temperature, plastic deformation, elastic recovery, and hardness were evaluated. The ex...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-015-2714-1
更新日期：2015-06-01 00:00:00
abstract：:The computational fragility spectra of atoms on the reaction path are presented for a selection of canonical processes represented by an amino group rotation around the (X)HC-NH(Y) bond (X = O, S; Y=H, CH3). Calculated spectra are found to very accurately describe the variation of atomic valence. Significant linear co...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-4029-0
更新日期：2019-04-26 00:00:00
abstract：:We propose a scheme to estimate hydrogen isotope effects on molecular polarizabilities. This approach combines the any-particle molecular orbital method, in which both electrons and H/D nuclei are described as quantum waves, with the auxiliary density perturbation theory, to calculate analytically the polarizability t...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3236-9
更新日期：2017-03-01 00:00:00
abstract：:Quantum chemical calculations using density functional theory BP86/def2-TZVPP and ab initio methods at CCSD(T)/def2-TZVPP have been carried for the telluroketones H2A=Te (A = C, Si, Ge). DFT calculations have also been carried out for the ketones H2C=E (E = O, S, Se, Te) and for the complexes NHC → [H2A=Te] → B(C6F5)3...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-014-2433-z
更新日期：2014-10-01 00:00:00
abstract：:A series of oligo(thienylenevinylene) derivatives with 1,4-dihydropyrrolo[3,2-b]pyrrole as core has been investigated at the PBE0/6-31G(d) and the TD-PBE0/6-31+G(d,p) levels to design materials with high performances such as broad absorption spectra and higher balance transfer property. The results show that position ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-013-1920-y
更新日期：2013-09-01 00:00:00
abstract：:There is a wide variety of ion channel types with various types of blockers, making research in this field very complicated. To reduce this complexity, it is essential to study ion channels and their blockers independently. Scorpion toxins, a major class of blockers, are charged short peptides with high affinities for...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-015-2822-y
更新日期：2015-11-01 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 structural, electronic, and optical features of quinoline derivatives were carried out by experiment and density functional theory (DFT). Our results show that a change in the substitution position of methyl group (CH3) gives rise to a decrease in the bandgap of quinoline derivatives from 2.75 to 2.5...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-020-04405-5
更新日期：2020-05-11 00:00:00
abstract：:DFT computations were carried out to characterize the (17)Oand (2)H electric field gradient, EFG, in various bisphosphonate derivatives. The computations were performed at the B3LYP level with 6-311++G (d,P) standard basis set. Calculated EFG tensors were used to determine the (17)O and (2)H nuclear quadrupole couplin...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-011-1114-4
更新日期：2012-03-01 00:00:00
abstract：:We design four high performance non-fullerene acceptor materials by applying strong electron withdrawing groups at the end of A-D-A-D-A type organic solar cells molecules and compute their different opto-electronic and photovoltaic properties, including absorption spectrum, electron density, solubility strength, charg...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-019-3932-8
更新日期：2019-01-31 00:00:00
abstract：:The geometries of three isomers of the C2H4O...2HF tri-molecular heterocyclic hydrogen-bonded complex were examined through B3LYP/aug-cc-pVDZ calculations. Analysis of structural parameters, determination of CHELPG (charge electrostatic potential grid) intermolecular charge transfer, interpretation of infrared stretch...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-008-0337-5
更新日期：2008-10-01 00:00:00
abstract：:Fruit softening is associated to cell wall modifications produced by a set of hydrolytic enzymes and proteins. Expansins are proteins with no catalytic activity, which have been associated with several processes during plant growth and development. A role for expansins has been proposed during softening of fruits, and...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-015-2656-7
更新日期：2015-05-01 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：:Adsorption of paracresol and water into the silicalite-1 (MFI) zeolite has been investigated using canonical and grand-canonical Monte Carlo simulations. The most stable sites of adsorption of paracresol are found to be located at the channel intersections. Grand-canonical simulations have shown that at low loading, w...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-008-0417-6
更新日期：2009-06-01 00:00:00
abstract：:Realistic molecular models of one and two-centre catalytic active sites originating from the cleavage of a precursor material known to give rise to an active double metal cyanide catalyst are described. Via periodic density functional calculations the structure of the proposed catalytic sites are shown to be dependent...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-007-0218-3
更新日期：2007-07-01 00:00:00
abstract：:Multi-tetrazole derivatives with conjugated structures were designed and investigated in this study. Using quantum chemistry methods, the crystal structures, electrostatic potentials (ESPs), multicenter bond orders, HOMO-LUMO energy gaps, and detonation properties of the derivatives were calculated. As expected, these...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-018-3710-z
更新日期：2018-06-23 00:00:00
abstract：:Prussian Blue is a paradigmatic mixed valence material and a parent compound to a broad family of electronically, optically, and magnetically active materials. Its exact composition varies greatly depending on the preparation route, leading to large variations in its electronic properties. The influence of water molec...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-008-0425-6
更新日期：2009-06-01 00:00:00
abstract：:To improve understanding of the unimolecular decomposition mechanism of 1,2,4-butanetriol trinitrate (BTTN) in the gas phase, density functional theory calculations were performed to determine various decomposition pathways at the B3LYP/6-311G** level. Two main mechanisms for the unimolecular decomposition of BTTN wer...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-014-2081-3
更新日期：2014-02-01 00:00:00
abstract：:Molecular dynamics simulations are conducted to investigate the buckling characteristics of functionalized carbon nanotubes (f-CNTs) under axial compression at various temperatures. The influences of functionalization, content of functional groups, chirality and diameter, as well as temperature on buckling response of...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-017-3505-7
更新日期：2017-11-04 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：:The mechanism of C-H bond activation of ethane was catalyzed by palladium halide cations (PdX+ (X = F, Cl, Br, H, and CH3)), which was investigated using density functional theory (DFT) at B3LYP level. The reaction mechanism was taken into account in triplet and singlet spin state potential energy surfaces. For PdF+, ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-020-04357-w
更新日期：2020-04-03 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：: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：:A theoretical study of the sulfur cumulenes SCnS (n = 3-8), CnS ( n = 1-8) and of their protonated forms (SCnS)H(+) and (CnS)H(+) that might exist in the interstellar environment, has been carried out by means of the standard B3LYP/6-311G** method. The geometries and relative energies of singlet and triplet states acc...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-014-2295-4
更新日期：2014-07-01 00:00:00
abstract：:The hydration free energies, structures, and dynamics of open- and closed-shell trivalent lanthanide and actinide metal cations are studied using molecular dynamics simulations (MD) based on a polarizable force field. Parameters for the metal cations are derived from an ab initio bottom-up strategy. MD simulations of ...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-014-2471-6
更新日期：2014-10-01 00:00:00
abstract：:The aim of the present work entitled electronic structure of PVA-PEG-Y2O3 (54 atom) is to present a theoretical study based on the hybrid function of three parameters Lee-Yang-Parr B3LYP of the density functional theory "DFT" quantum mechanical approach together with LanL2DZ basis sets for optoelectronics applications...
journal_title：Journal of molecular modeling
pub_type： 杂志文章
doi：10.1007/s00894-020-04479-1
更新日期：2020-07-20 00:00:00
