scholarly journals Specific interactions between DNA and regulatory protein controlled by ligand-binding: Ab initio molecular simulation

2015 ◽  
Author(s):  
Y. Matsushita ◽  
T. Murakawa ◽  
K. Shimamura ◽  
M. Oishi ◽  
T. Ohyama ◽  
...  
Keyword(s):  
Ligand Binding ◽  
Ab Initio ◽  
Molecular Simulation ◽  
Regulatory Protein ◽  
Specific Interactions

scholarly journals Suramin Targets the Conserved Ligand-Binding Pocket of Human Raf1 Kinase Inhibitory Protein

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1151
Author(s):  
Chenyun Guo ◽  
Zhihua Wu ◽  
Weiliang Lin ◽  
Hao Xu ◽  
Ting Chang ◽  
...  
Keyword(s):  
Side Effects ◽  
Ligand Binding ◽  
Mapk Pathway ◽  
Regulatory Protein ◽  
Therapeutic Index ◽  
Binding Pocket ◽  
Biological Macromolecules ◽  
Inhibitory Protein ◽  
Ligand Binding Pocket ◽  
Raf1 Kinase

Suramin was initially used to treat African sleeping sickness and has been clinically tested to treat human cancers and HIV infection in the recent years. However, the therapeutic index is low with numerous clinical side-effects, attributed to its diverse interactions with multiple biological macromolecules. Here, we report a novel binding target of suramin, human Raf1 kinase inhibitory protein (hRKIP), which is an important regulatory protein involved in the Ras/Raf1/MEK/ERK (MAPK) signal pathway. Biolayer interference technology showed that suramin had an intermediate affinity for binding hRKIP with a dissociation constant of 23.8 µM. Both nuclear magnetic resonance technology and molecular docking analysis revealed that suramin bound to the conserved ligand-binding pocket of hRKIP, and that residues K113, W173, and Y181 play crucial roles in hRKIP binding suramin. Furthermore, suramin treatment at 160 µM could profoundly increase the ERK phosphorylation level by around 3 times. Our results indicate that suramin binds to hRKIP and prevents hRKIP from binding with hRaf1, thus promoting the MAPK pathway. This work is beneficial to both mechanistically understanding the side-effects of suramin and efficiently improving the clinical applications of suramin.

Specific interactions between mycobacterial FtsZ protein and curcumin derivatives: Molecular docking and ab initio molecular simulations

2018 ◽  
Vol 692 ◽  
pp. 166-173 ◽  
Author(s):  
Mitsuki Fujimori ◽  
Haruki Sogawa ◽  
Shintaro Ota ◽  
Pavel Karpov ◽  
Sergey Shulga ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Ab Initio ◽  
Molecular Simulations ◽  
Specific Interactions ◽  
Curcumin Derivatives ◽  
Ftsz Protein

scholarly journals Proteomic analysis and molecular modelling characterize the iron-regulatory protein haemojuvelin/repulsive guidance molecule c

2013 ◽  
Vol 452 (1) ◽  
pp. 87-95 ◽  
Author(s):  
Mahta Nili ◽  
Larry David ◽  
Johannes Elferich ◽  
Ujwal Shinde ◽  
Peter Rotwein
Keyword(s):  
Ab Initio ◽  
Molecular Modelling ◽  
Electron Transfer Dissociation ◽  
Structural Information ◽  
Regulatory Protein ◽  
Structural Features ◽  
Single Chain ◽  
Disulfide Linkages ◽  
Repulsive Guidance Molecule ◽  
Guidance Molecule

HJV (haemojuvelin) plays a key role in iron metabolism in mammals by regulating expression of the liver-derived hormone hepcidin, which controls systemic iron uptake and release. Mutations in HJV cause juvenile haemochromatosis, a rapidly progressing iron overload disorder in humans. HJV, also known as RGMc (repulsive guidance molecule c), is a member of the three-protein RGM family. RGMs are GPI (glycosylphosphatidylinositol)-linked glycoproteins that share ~50% amino acid identity and several structural motifs, including the presence of 14 cysteine residues in analogous locations. Unlike RGMa and RGMb, HJV/RGMc is composed of both single-chain and two-chain isoforms. To date there is no structural information for any member of the RGM family. In the present study we have mapped the disulfide bonds in mouse HJV/RGMc using a proteomics strategy combining sequential MS steps composed of ETD (electron transfer dissociation) and CID (collision-induced dissociation), in which ETD induces cleavage of disulfide linkages, and CID establishes disulfide bond assignments between liberated peptides. The results of the present study identified an HJV/RGMc molecular species containing four disulfide linkages. We predict using ab initio modelling that this molecule is a single-chain HJV/RGMc isoform. Our observations outline a general approach using tandem MS and ab initio molecular modelling to define unknown structural features in proteins.

An Estimation of Thermodynamic and Transport Properties of Cryogenic Hydrogen Using Classical Molecular Simulation

2011 ◽  
Author(s):  
Hiroki Nagashima ◽  
Takashi Tokumasu ◽  
Shin-ichi Tsuda ◽  
Nobuyuki Tsuboi ◽  
Mitsuo Koshi ◽  
...  
Keyword(s):  
Ab Initio ◽  
Transport Properties ◽  
Molecular Simulation ◽  
Potential Model ◽  
Classical Method ◽  
Quantum Effect ◽  
Corresponding States ◽  
Density Region ◽  
Lennard Jones ◽  
Thermodynamic And Transport Properties

In this paper, we estimated the thermodynamic and transport properties of cryogenic hydrogen using classical molecular simulation to clarify the limit of classical method on the estimation of those properties of cryogenic hydrogen. Three empirical potentials, the Lennard-Jones (LJ) potential, two-center Lennard-Jones (2CLJ) potential, and modified Buckingham (exp-6) potential, and an ab initio potential model derived by the molecular orbital (MO) calculation were applied. Molecular dynamics (MD) simulations were performed across a wide density-temperature range. Using these data, the equation of state (EOS) was obtained by Kataoka’s method, and these were compared with NIST (National Institute of Standards and Technology) data according to the principle of corresponding states. Moreover, we investigated transport coefficients (viscosity coefficient, diffusion coefficient and thermal conductivity) using time correlation function. As a result, it was confirmed that the potential model has a large effect on the estimated thermodynamic and transport properties of cryogenic hydrogen. On the other hand, from the viewpoint of the principle of corresponding states, we obtained the same results from the empirical potential models as from the ab initio potential, showing that the potential model has only a small effect on the reduced EOS: the classical MD results could not reproduce the NIST data in the high-density region. This difference is thought to arise from the quantum effect in actual liquid hydrogen.

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