Effects of Pooling Operations on Prediction of Ligand Rotation‐Dependent Protein–Ligand Binding in 3D Graph Convolutional Network

2021 ◽  
Author(s):  
Yeji Kim ◽  
Jihoo Kim ◽  
Won June Kim ◽  
Eok Kyun Lee ◽  
Insung S. Choi
Keyword(s):  
Ligand Binding ◽  
Convolutional Network ◽  
Dependent Protein

scholarly journals Combinatorial design of chemical-dependent protein switches for controlling intracellular electron transfer

2019 ◽  
Author(s):  
Bingyan Wu ◽  
Joshua T. Atkinson ◽  
Dimithree Kahanda ◽  
George. N. Bennett ◽  
Jonathan J. Silberg
Keyword(s):  
Electron Transfer ◽  
Ligand Binding ◽  
Fusion Proteins ◽  
Electron Flow ◽  
Combinatorial Design ◽  
Human Estrogen Receptor ◽  
Dependent Protein ◽  
Insertion Sites ◽  
Domain Insertion ◽  
Bacterial Selection

ABSTRACTOne challenge with controlling electron flow in cells is the lack of biomolecules that directly couple the sensing of environmental conditions to electron transfer efficiency. To overcome this protein component limitation, we randomly inserted the ligand binding domain (LBD) from the human estrogen receptor (ER) into a thermostable 2Fe-2S ferredoxin (Fd) from Mastigocladus laminosus and used a bacterial selection to identify Fd-LBD fusion proteins that support electron transfer from a Fd-NADP reductase (FNR) to a Fd-dependent sulfite reductase (SIR). Mapping LBD insertion sites onto structure revealed that Fd tolerates domain insertion adjacent to or within the tetracysteine motif that coordinates the 2Fe-2S metallocluster. With both classes of the fusion proteins, cellular ET was enhanced by the ER antagonist 4-hydroxytamoxifen. In addition, one of Fds arising from ER-LBD insertion within the tetracysteine motif acquires an oxygen-tolerant 2Fe-2S cluster, suggesting that ET is regulated through post-translational ligand binding.

scholarly journals A Cascade Graph Convolutional Network for Predicting Protein–Ligand Binding Affinity

2021 ◽  
Vol 22 (8) ◽  
pp. 4023
Author(s):  
Huimin Shen ◽  
Youzhi Zhang ◽  
Chunhou Zheng ◽  
Bing Wang ◽  
Peng Chen
Keyword(s):  
Neural Network ◽  
Ligand Binding ◽  
Convolutional Neural Network ◽  
Binding Affinity ◽  
Network Architecture ◽  
Original Data ◽  
Ligand Complex ◽  
Convolutional Network ◽  
Data Set ◽  
Irregular Data

Accurate prediction of binding affinity between protein and ligand is a very important step in the field of drug discovery. Although there are many methods based on different assumptions and rules do exist, prediction performance of protein–ligand binding affinity is not satisfactory so far. This paper proposes a new cascade graph-based convolutional neural network architecture by dealing with non-Euclidean irregular data. We represent the molecule as a graph, and use a simple linear transformation to deal with the sparsity problem of the one-hot encoding of original data. The first stage adopts ARMA graph convolutional neural network to learn the characteristics of atomic space in the protein–ligand complex. In the second stage, one variant of the MPNN graph convolutional neural network is introduced with chemical bond information and interactive atomic features. Finally, the architecture passes through the global add pool and the fully connected layer, and outputs a constant value as the predicted binding affinity. Experiments on the PDBbind v2016 data set showed that our method is better than most of the current methods. Our method is also comparable to the state-of-the-art method on the data set, and is more intuitive and simple.

scholarly journals Proton Sensitivity of Corticotropin-Releasing Hormone Receptor 1 Signaling to Proopiomelanocortin in Male Mice

Endocrinology ◽  
2018 ◽  
Vol 160 (2) ◽  
pp. 276-291 ◽  
Author(s):  
Hiraku Kameda ◽  
Masaaki Yamamoto ◽  
Yukiko Tone ◽  
Masahide Tone ◽  
Shlomo Melmed
Keyword(s):  
Ligand Binding ◽  
Low Ph ◽  
Pituitary Cells ◽  
Dependent Protein Kinase ◽  
Ectopic Acth ◽  
Primary Mouse ◽  
Dependent Protein ◽  
Acidic Conditions ◽  
Mouse Pituitary ◽  
The Impact

Abstract Because an acidic cellular microenvironment is engendered by inflammation and may determine cell differentiation, we elucidated the impact of acidic conditions on induction of proopiomelanocortin (POMC) expression. Here, we demonstrate mechanisms for proton sensitivity of CRH receptor 1 (CRHR1) signaling to POMC and ACTH production. Low pH (6.8) resulted in doubling of POMC expression and ACTH production in pituitary cell line AtT-20 and in primary mouse pituitary cells. Using CRISPR knockout, we show that CRHR1 is necessary for acid-induced POMC expression, and this induction is mediated by CRHR1 histidine residues and calmodulin-dependent protein kinase II in both pituitary corticotroph cells and in nonpituitary cell lines expressing ectopic ACTH. In contrast, CRH ligand binding affinity to CRHR1 was decreased with acidic pH, implying that proton-induced POMC expression prevails in acidic conditions independently of CRH ligand binding. The results indicate that proton-induced CRHR1 signaling regulates ACTH production in response to an acidic microenvironment.

scholarly journals Conformational signaling required for synaptic plasticity by the NMDA receptor complex

2015 ◽  
Vol 112 (47) ◽  
pp. 14711-14716 ◽  
Author(s):  
Jonathan Aow ◽  
Kim Dore ◽  
Roberto Malinow
Keyword(s):  
Synaptic Plasticity ◽  
Nmda Receptor ◽  
Ligand Binding ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Dependent Protein Kinase ◽  
Ion Flow ◽  
Calcium Calmodulin Dependent ◽  
Nmda Receptor Complex ◽  
Dependent Protein

The NMDA receptor (NMDAR) is known to transmit important information by conducting calcium ions. However, some recent studies suggest that activation of NMDARs can trigger synaptic plasticity in the absence of ion flow. Does ligand binding transmit information to signaling molecules that mediate synaptic plasticity? Using Förster resonance energy transfer (FRET) imaging of fluorescently tagged proteins expressed in neurons, conformational signaling is identified within the NMDAR complex that is essential for downstream actions. Ligand binding transiently reduces FRET between the NMDAR cytoplasmic domain (cd) and the associated protein phosphatase 1 (PP1), requiring NMDARcd movement, and persistently reduces FRET between the NMDARcd and calcium/calmodulin-dependent protein kinase II (CaMKII), a process requiring PP1 activity. These studies directly monitor agonist-driven conformational signaling at the NMDAR complex required for synaptic plasticity.

Determinants of Ligand Binding to cAMP-Dependent Protein Kinase†

Biochemistry ◽  
1999 ◽  
Vol 38 (8) ◽  
pp. 2358-2366 ◽  
Author(s):  
Philippe H. Hünenberger ◽  
Volkhard Helms ◽  
Narendra Narayana ◽  
Susan S. Taylor ◽  
J. Andrew McCammon
Keyword(s):  
Protein Kinase ◽  
Ligand Binding ◽  
Dependent Protein Kinase ◽  
Camp Dependent Protein Kinase ◽  
Dependent Protein

CarR, a MarR-family regulator from Corynebacterium glutamicum, modulated antibiotic and aromatic compound resistance

2019 ◽  
Vol 476 (21) ◽  
pp. 3141-3159 ◽  
Author(s):  
Meiru Si ◽  
Can Chen ◽  
Zengfan Wei ◽  
Zhijin Gong ◽  
GuiZhi Li ◽  
...  
Keyword(s):  
Stress Response ◽  
Ligand Binding ◽  
Corynebacterium Glutamicum ◽  
Conformational Changes ◽  
Cysteine Oxidation ◽  
Transcriptional Regulatory ◽  
Ligand Free ◽  
Redox Sensing

Abstract MarR (multiple antibiotic resistance regulator) proteins are a family of transcriptional regulators that is prevalent in Corynebacterium glutamicum. Understanding the physiological and biochemical function of MarR homologs in C. glutamicum has focused on cysteine oxidation-based redox-sensing and substrate metabolism-involving regulators. In this study, we characterized the stress-related ligand-binding functions of the C. glutamicum MarR-type regulator CarR (C. glutamicum antibiotic-responding regulator). We demonstrate that CarR negatively regulates the expression of the carR (ncgl2886)–uspA (ncgl2887) operon and the adjacent, oppositely oriented gene ncgl2885, encoding the hypothetical deacylase DecE. We also show that CarR directly activates transcription of the ncgl2882–ncgl2884 operon, encoding the peptidoglycan synthesis operon (PSO) located upstream of carR in the opposite orientation. The addition of stress-associated ligands such as penicillin and streptomycin induced carR, uspA, decE, and PSO expression in vivo, as well as attenuated binding of CarR to operator DNA in vitro. Importantly, stress response-induced up-regulation of carR, uspA, and PSO gene expression correlated with cell resistance to β-lactam antibiotics and aromatic compounds. Six highly conserved residues in CarR were found to strongly influence its ligand binding and transcriptional regulatory properties. Collectively, the results indicate that the ligand binding of CarR induces its dissociation from the carR–uspA promoter to derepress carR and uspA transcription. Ligand-free CarR also activates PSO expression, which in turn contributes to C. glutamicum stress resistance. The outcomes indicate that the stress response mechanism of CarR in C. glutamicum occurs via ligand-induced conformational changes to the protein, not via cysteine oxidation-based thiol modifications.

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