scholarly journals Binding of propene on small gold clusters and on Au(111): Simple rules for binding sites and relative binding energies

2004 ◽  
Vol 121 (8) ◽  
pp. 3756-3766 ◽  
Author(s):  
Steeve Chrétien ◽  
Mark S. Gordon ◽  
Horia Metiu
Keyword(s):  
Binding Sites ◽  
Gold Clusters ◽  
Binding Energies ◽  
Relative Binding ◽  
Simple Rules

Cationic gold clusters ligated with differently substituted phosphines: effect of substitution on ligand reactivity and binding

2015 ◽  
Vol 17 (22) ◽  
pp. 14636-14646 ◽  
Author(s):  
Grant E. Johnson ◽  
Astrid Olivares ◽  
David Hill ◽  
Julia Laskin
Keyword(s):  
Ligand Binding ◽  
Lone Pair ◽  
Gold Clusters ◽  
Binding Energies ◽  
Phosphine Ligands ◽  
Strongly Correlated ◽  
P Loss ◽  
Ligand Reactivity ◽  
Cationic Gold

Loss of substituted phosphine ligands is strongly correlated with the electron donating ability of the phosphorous lone pair. The results indicate that the relative ligand binding energies increase in the order PMe3 < PPhMe2 < PPh2Me < PPh3 < PPh2Cy < PPhCy2 < PCy3.

scholarly journals Inferring Binding Energies from Selected Binding Sites

2009 ◽  
Vol 5 (12) ◽  
pp. e1000590 ◽  
Author(s):  
Yue Zhao ◽  
David Granas ◽  
Gary D. Stormo
Keyword(s):  
Binding Sites ◽  
Binding Energies

scholarly journals The Relative Binding Position of Nck and Grb2 Adaptors Dramatically Impacts Actin-Based Motility of Vaccinia Virus

2021 ◽  
Author(s):  
Angika Basant ◽  
Michael Way
Keyword(s):  
Vaccinia Virus ◽  
Binding Sites ◽  
Actin Polymerization ◽  
Cellular Processes ◽  
Viral Spread ◽  
Relative Binding ◽  
Signal Output ◽  
Signalling Cascade ◽  
Binding Position

ABSTRACTPhosphotyrosine (pTyr) motifs in unstructured polypeptides orchestrate important cellular processes by engaging SH2-containing adaptors to nucleate complex signalling networks. The concept of phase separation has recently changed our appreciation of such multivalent networks, however, the role of pTyr motif positioning in their function remains to be explored. We have now explored this parameter in the assembly and operation of the signalling cascade driving actin-based motility and spread of Vaccinia virus. This network involves two pTyr motifs in the viral protein A36 that recruit the adaptors Nck and Grb2 upstream of N-WASP and Arp2/3-mediated actin polymerization. We generated synthetic networks on Vaccinia by manipulating pTyr motifs in A36 and the unrelated p14 from Orthoreovirus. In contrast to predictions, we find that only specific spatial arrangements of Grb2 and Nck binding sites result in robust N-WASP recruitment, Arp2/3 driven actin polymerization and viral spread. Our results suggest that the relative position of pTyr adaptor binding sites is optimised for signal output. This finding may explain why the relative positions of pTyr motifs are usually conserved in proteins from widely different species. It also has important implications for regulation of physiological networks, including those that undergo phase transitions.

scholarly journals Polypharmacological study of Ceritinib using a structure based in silico approach

Bionatura ◽  
2019 ◽  
Vol 4 (2) ◽  
pp. 836-840
Author(s):  
Tammanna R. Sahrawat ◽  
Prabhjeet Kaur Kaur
Keyword(s):  
Side Effects ◽  
Binding Sites ◽  
In Silico ◽  
Protein Tyrosine Kinase ◽  
Drug Repurposing ◽  
Aurora Kinase ◽  
Specific Protein ◽  
Binding Energies ◽  
Aurora Kinase B ◽  
Anaplastic Lymphoma

Drug repurposing has gained mass recognition over the past few years as it has paved new therapeutic applications for already approved FDA drugs. It focuses on finding new molecular targets of drugs for medical uses different than the one originally proposed. Ceritinib, an Anaplastic Lymphoma Kinase (ALK) inhibitor is given orally in the treatment of non-small cell lung cancer (NSCLC). This treatment has been reported to be associated with a number of side effects such as hyperglycemia, convulsion, pneumonitis etc. The side effects are usually due to the unintended interaction of the drug with other protein targets. In silico polypharmacological studies of Ceritinib suggests that it binds to multiple targets other than the intended one which may largely be due to different proteins possessing similar binding sites. ProBis server was used to retrieve probable off-targets of Ceritinib based on presence of structurally similar protein binding sites as that of ALK. Ceritinib was found to bind effectively to three proteins namely Lymphocyte Cell-Specific Protein-Tyrosine Kinase, Tropomyosin receptor kinase B and Aurora kinase B having favorable binding energies and inhibition constants, with no reported side-effects as compared to their marketed drugs. Therefore, it is concluded from the present study that Ceritinib may act as an effective therapeutic target against its polypharmacological targets.

scholarly journals IDH1 and IDH2 mutants identified in cancer lose inhibition by isocitrate because of a change in their binding sites

2018 ◽  
Author(s):  
Juan P. Bascur ◽  
Melissa Alegría-Arcos ◽  
Ingrid Araya-Durán ◽  
Ezequiel I. Juritz ◽  
Fernando D. González-Nilo ◽  
...  
Keyword(s):  
Molecular Docking ◽  
Binding Sites ◽  
Competitive Inhibition ◽  
Binding Energies ◽  
Substrate Affinity ◽  
Wild Type ◽  
Similarity Estimation ◽  
In The Wild ◽  
Docking Calculations ◽  
Idh1 And Idh2 Mutations

AbstractIDH1 and IDH2 are human enzymes that convert isocitrate (ICT) into α-ketoglutarate (AKG). However, mutations in positions R132 of IDH1 and R140 and R172 of IDH2 cause these enzymes to convert AKG into 2-hydroxyglutarate (2HG). Concurrently, accumulation of 2HG in the cell is correlated with the development of cancer. This activity change is mainly due to the loss of the competitive inhibition by ICT of these enzymes, but the molecular mechanism behind this loss of inhibition is currently unknown. In this work we characterized the inhibition and loss of inhibition of IDH1 and IDH2 by means of the binding energies derived from molecular docking calculations. We characterized the substrate binding sites and how they differ among the mutant and wild type enzymes using a Jaccard similarity coefficient based on the residues involved in binding the substrates. We found that molecular docking effectively identifies the inhibition by ICT in the wild type and mutant enzymes that do not appear in tumors, and the loss of inhibition in the mutant enzymes that appear in tumors. Additionally, we found that the binding sites of the mutant enzymes are different among themselves. Finally, we found that the regulatory segment of IDH1 plays a prominent role in the change of binding sites between the mutant enzymes and the wild-type enzymes. Our findings show that the loss of inhibition is related to variations in the enzyme binding sites. Additionally, our findings show that a drug capable of targeting all IDH1 and IDH2 mutations in cancer is unlikely to be found due to significant differences among the binding sites of these paralogs. Moreover, the methodology developed here, which combines molecular docking calculations with binding site similarity estimation, can be useful for engineering enzymes, for instance, when aiming to modify the substrate affinity of an enzyme.

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