scholarly journals Probing backbone hydrogen bonding in PDZ/ligand interactions by protein amide-to-ester mutations

2014 ◽  
Vol 5 (1) ◽  
Author(s):  
Søren W. Pedersen ◽  
Stine B. Pedersen ◽  
Louise Anker ◽  
Greta Hultqvist ◽  
Anders S. Kristensen ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Ligand Interactions

scholarly journals Relevance of Hydrogen Bonds for the Histamine H2 Receptor-Ligand Interactions: A Lesson from Deuteration

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 196 ◽  
Author(s):  
Mojca Kržan ◽  
Jan Keuschler ◽  
Janez Mavri ◽  
Robert Vianello
Keyword(s):  
Hydrogen Bonding ◽  
Active Sites ◽  
Density Functional ◽  
Receptor Activation ◽  
Histamine H2 Receptor ◽  
Therapeutic Practice ◽  
H2 Receptor ◽  
Ligand Interactions ◽  
Solvent Molecules ◽  
Near Future

We used a combination of density functional theory (DFT) calculations and the implicit quantization of the acidic N–H and O–H bonds to assess the effect of deuteration on the binding of agonists (2-methylhistamine and 4-methylhistamine) and antagonists (cimetidine and famotidine) to the histamine H2 receptor. The results show that deuteration significantly increases the affinity for 4-methylhistamine and reduces it for 2-methylhistamine, while leaving it unchanged for both antagonists, which is found in excellent agreement with experiments. The revealed trends are interpreted in the light of the altered strength of the hydrogen bonding upon deuteration, known as the Ubbelohde effect, which affects ligand interactions with both active sites residues and solvent molecules preceding the binding, thus providing strong evidence for the relevance of hydrogen bonding for this process. In addition, computations further underline an important role of the Tyr250 residue for the binding. The obtained insight is relevant for the therapy in the context of (per)deuterated drugs that are expected to enter therapeutic practice in the near future, while this approach may contribute towards understanding receptor activation and its discrimination between agonists and antagonists.

A facile strategy to fabricate highly-stretchable self-healing poly(vinyl alcohol) hybrid hydrogels based on metal–ligand interactions and hydrogen bonding

2016 ◽  
Vol 7 (47) ◽  
pp. 7269-7277 ◽  
Author(s):  
Yan Hui ◽  
Zhi-Bin Wen ◽  
Florence Pilate ◽  
Hui Xie ◽  
Cheng-Jie Fan ◽  
...  
Keyword(s):  
Hydrogen Bonding ◽  
Vinyl Alcohol ◽  
Poly Vinyl Alcohol ◽  
Self Healing ◽  
Hybrid Hydrogel ◽  
Hybrid Hydrogels ◽  
Ligand Interactions ◽  
Highly Stretchable ◽  
Metal Ligand

A novel poly(vinyl alcohol) hybrid hydrogel based on metal–ligand interactions and hydrogen bonding was fabricated, possessing highly-stretchable and self-healing properties.

scholarly journals Identification of a novel inhibitor of SARS-CoV-2 3CL-PRO through virtual screening and molecular dynamics simulation

PeerJ ◽  
2021 ◽  
Vol 9 ◽  
pp. e11261
Author(s):  
Asim Kumar Bepari ◽  
Hasan Mahmud Reza
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bonding ◽  
Virtual Screening ◽  
Molecular Dynamics Simulations ◽  
Mean Square ◽  
Autodock Vina ◽  
Protein Ligand Interactions ◽  
Main Protease ◽  
Ligand Interactions ◽  
Dynamics Simulations

Background The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has ravaged lives across the globe since December 2019, and new cases are still on the rise. Peoples’ ongoing sufferings trigger scientists to develop safe and effective remedies to treat this deadly viral disease. While repurposing the existing FDA-approved drugs remains in the front line, exploring drug candidates from synthetic and natural compounds is also a viable alternative. This study employed a comprehensive computational approach to screen inhibitors for SARS-CoV-2 3CL-PRO (also known as the main protease), a prime molecular target to treat coronavirus diseases. Methods We performed 100 ns GROMACS molecular dynamics simulations of three high-resolution X-ray crystallographic structures of 3CL-PRO. We extracted frames at 10 ns intervals to mimic conformational diversities of the target protein in biological environments. We then used AutoDock Vina molecular docking to virtual screen the Sigma–Aldrich MyriaScreen Diversity Library II, a rich collection of 10,000 druglike small molecules with diverse chemotypes. Subsequently, we adopted in silico computation of physicochemical properties, pharmacokinetic parameters, and toxicity profiles. Finally, we analyzed hydrogen bonding and other protein-ligand interactions for the short-listed compounds. Results Over the 100 ns molecular dynamics simulations of 3CL-PRO’s crystal structures, 6LZE, 6M0K, and 6YB7, showed overall integrity with mean Cα root-mean-square deviation (RMSD) of 1.96 (±0.35) Å, 1.98 (±0.21) Å, and 1.94 (±0.25) Å, respectively. Average root-mean-square fluctuation (RMSF) values were 1.21 ± 0.79 (6LZE), 1.12 ± 0.72 (6M0K), and 1.11 ± 0.60 (6YB7). After two phases of AutoDock Vina virtual screening of the MyriaScreen Diversity Library II, we prepared a list of the top 20 ligands. We selected four promising leads considering predicted oral bioavailability, druglikeness, and toxicity profiles. These compounds also demonstrated favorable protein-ligand interactions. We then employed 50-ns molecular dynamics simulations for the four selected molecules and the reference ligand 11a in the crystallographic structure 6LZE. Analysis of RMSF, RMSD, and hydrogen bonding along the simulation trajectories indicated that S51765 would form a more stable protein-ligand complexe with 3CL-PRO compared to other molecules. Insights into short-range Coulombic and Lennard-Jones potentials also revealed favorable binding of S51765 with 3CL-PRO. Conclusion We identified a potential lead for antiviral drug discovery against the SARS-CoV-2 main protease. Our results will aid global efforts to find safe and effective remedies for COVID-19.

Self-healing and shape-memory properties of polymeric materials cross-linked by hydrogen bonding and metal–ligand interactions

2019 ◽  
Vol 10 (33) ◽  
pp. 4519-4523 ◽  
Author(s):  
Yuichiro Kobayashi ◽  
Tomohiro Hirase ◽  
Yoshinori Takashima ◽  
Akira Harada ◽  
Hiroyasu Yamaguchi
Keyword(s):  
Hydrogen Bonding ◽  
Shape Memory ◽  
Polymeric Materials ◽  
Cross Linking ◽  
Self Healing ◽  
Shape Memory Properties ◽  
Ligand Interactions ◽  
Non Covalent Interactions ◽  
Covalent Interactions ◽  
Metal Ligand

Polymeric materials were prepared by cross-linking them with two independent non-covalent interactions, namely hydrogen bonding and metal–ligand interactions.

New insights into heparan sulphate biosynthesis from the study of mutant mice

2002 ◽  
Vol 69 ◽  
pp. 47-57 ◽  
Author(s):  
Catherine L. R. Merry ◽  
John T. Gallagher
Keyword(s):  
Growth Factors ◽  
Biosynthetic Pathway ◽  
Heparan Sulphate ◽  
Mutant Mice ◽  
Gene Products ◽  
Multiple Gene ◽  
Adhesion Proteins ◽  
Ligand Interactions

Heparan sulphate (HS) is an essential co-receptor for a number of growth factors, morphogens and adhesion proteins. The biosynthetic modifications involved in the generation of a mature HS chain may determine the strength and outcome of HS–ligand interactions. These modifications are catalysed by a complex family of enzymes, some of which occur as multiple gene products. Various mutant mice have now been generated, which lack the function of isolated components of the HS biosynthetic pathway. In this discussion, we outline the key findings of these studies, and use them to put into context our own work concerning the structure of the HS generated by the Hs2st-/- mice.

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