scholarly journals Energy and Reactivity Profile and Proton Affinity Analysis of Rimegepant with Special Reference to its Potential Activity against SARS-Cov-2 Virus Proteins using Molecular Dynamics

2021 ◽  
Author(s):  
T Pooventhiran ◽  
Ephraim Felix Marondedze ◽  
Penny Poomani Govender ◽  
Utsab Bhattacharyya ◽  
D Jagadeeswara Rao ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Hydrophobic Interactions ◽  
Chemical Properties ◽  
Basis Set ◽  
Basis Sets ◽  
Implicit Solvent ◽  
B3lyp Functional ◽  
Potential Activity ◽  
Dynamics Simulations ◽  
Physical And Chemical

Abstract Rimegepant is a new medicine developed for the management of chronic headache due to migraine. This manuscript is an attempt to study the various structural, physical and chemical properties of the molecules. The molecule was optimised using B3LYP functional with 6-311G+(2d,p) basis set. Excited state properties of the compound were studied using CAM-B3LYP functional with same basis sets using IEFPCM model in methanol for the implicit solvent atmosphere. The various electronic descriptors helped to identify the reactivity behaviour and stability. The compound is found to possess good nonlinear optical properties in gas phase. The various intramolecular electronic delocalisations and non-covalent interactions were analysed and explained. As the compound contain several heterocyclic nitrogen atoms, they have potential proton abstraction features, which was analysed energetically. The most important result from this study is from the molecular docking analysis which indicates that rimegepant binds irreversibly with three established SARS-CoV-2 proteins with ID 6LU7, 6M03 and 6W63 with docking scores − 9.2988, -8.3629 and − 9.5421 kcal/mol respectively. Further assessment of docked complexes with molecular dynamics simulations revealed that hydrophobic interactions, water bridges and π – π interactions play a signification role in stabilising the ligand within the binding region of respective proteins. MMGBSA free energies further demonstrated that rimegepant is more stable when complexed with 6LU7 among the selected PDB models. As the pharmacology and pharmacokinetics of this molecule are already established, rimegepant can be considered as an ideal candidate with potential for use in the treatment of COVID patients after clinical studies.

Probing the binding mechanism of polybrominated diphenyl ethers with transthyretin by multi-spectroscopic and molecular dynamics simulations

2017 ◽  
Vol 9 (26) ◽  
pp. 3929-3940 ◽  
Author(s):  
Jie Xu ◽  
Zhongsheng Yi ◽  
Yuchen Wei ◽  
Wu Yang ◽  
Lulu Yang ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Polybrominated Diphenyl Ethers ◽  
Chemical Properties ◽  
Physical And Chemical Properties ◽  
Binding Mechanism ◽  
Diphenyl Ethers ◽  
Dynamics Simulations ◽  
Physical And Chemical ◽  
And Chemical Properties

The physical and chemical properties of polybrominated diphenyl ethers (PBDEs) are important for modeling their transport.

scholarly journals Lecithin as a Putative Biodegradable Blocker of SARS-CoV-2

2020 ◽  
Author(s):  
Muhammad Nawaz Qaisrani ◽  
Jawad Ur Rehman ◽  
Roman Belousov ◽  
Elham Moharramzadeh Goliaei ◽  
Ivan Girotto ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Hydrophobic Interactions ◽  
Chemical Properties ◽  
Binding Motif ◽  
Proof Of Concept ◽  
Angiotensin Converting Enzyme 2 ◽  
Preferential Binding ◽  
Dynamics Simulations ◽  
Physical And Chemical ◽  
And Chemical Properties

<p>Understanding the physical and chemical properties of viral infection at molecular scales is a major challenge of the scientific community in the fight against the Coronavirus (COVID-19) pandemic. We employ all-atoms molecular dynamics simulations to study the interaction between the receptor-binding domain of the SARS-CoV-2 spike protein and the surfactant lecithin in water solutions. Our microsecond simulations reveal a preferential binding of lecithin to the receptor-binding motif (RBM) of SARS-CoV-2. Furthermore, we find that the lecitin-RBM binding events are mainly dominated by the hydrophobic interactions, which are accompanied by dewetting of water molecules near the RBM. These proof-of-concept simulations provide a demonstration of the use of biodegradable phospholipids as blockers of binding of SARS-CoV-2 with the human Angiotensin-Converting Enzyme 2 (ACE2) receptor.</p>

scholarly journals Lecithin as a Putative Biodegradable Blocker of SARS-CoV-2

2020 ◽  
Author(s):  
Muhammad Nawaz Qaisrani ◽  
Jawad Ur Rehman ◽  
Roman Belousov ◽  
Elham Moharramzadeh Goliaei ◽  
Ivan Girotto ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Hydrophobic Interactions ◽  
Chemical Properties ◽  
Binding Motif ◽  
Proof Of Concept ◽  
Angiotensin Converting Enzyme 2 ◽  
Preferential Binding ◽  
Dynamics Simulations ◽  
Physical And Chemical ◽  
And Chemical Properties

<p>Understanding the physical and chemical properties of viral infection at molecular scales is a major challenge of the scientific community in the fight against the Coronavirus (COVID-19) pandemic. We employ all-atoms molecular dynamics simulations to study the interaction between the receptor-binding domain of the SARS-CoV-2 spike protein and the surfactant lecithin in water solutions. Our microsecond simulations reveal a preferential binding of lecithin to the receptor-binding motif (RBM) of SARS-CoV-2. Furthermore, we find that the lecitin-RBM binding events are mainly dominated by the hydrophobic interactions, which are accompanied by dewetting of water molecules near the RBM. These proof-of-concept simulations provide a demonstration of the use of biodegradable phospholipids as blockers of binding of SARS-CoV-2 with the human Angiotensin-Converting Enzyme 2 (ACE2) receptor.</p>

scholarly journals Lecithin as a Putative Biodegradable Blocker of SARS-CoV-2

2020 ◽  
Author(s):  
Muhammad Nawaz Qaisrani ◽  
Jawad Ur Rehman ◽  
Roman Belousov ◽  
Elham Moharramzadeh Goliaei ◽  
Ivan Girotto ◽  
...  
Keyword(s):  
Receptor Binding ◽  
Hydrophobic Interactions ◽  
Chemical Properties ◽  
Binding Motif ◽  
Proof Of Concept ◽  
Angiotensin Converting Enzyme 2 ◽  
Preferential Binding ◽  
Dynamics Simulations ◽  
Physical And Chemical ◽  
And Chemical Properties

<p>Understanding the physical and chemical properties of viral infection at molecular scales is a major challenge of the scientific community in the fight against the Coronavirus (COVID-19) pandemic. We employ all-atoms molecular dynamics simulations to study the interaction between the receptor-binding domain of the SARS-CoV-2 spike protein and the surfactant lecithin in water solutions. Our microsecond simulations reveal a preferential binding of lecithin to the receptor-binding motif (RBM) of SARS-CoV-2. Furthermore, we find that the lecitin-RBM binding events are mainly dominated by the hydrophobic interactions, which are accompanied by dewetting of water molecules near the RBM. These proof-of-concept simulations provide a demonstration of the use of biodegradable phospholipids as blockers of binding of SARS-CoV-2 with the human Angiotensin-Converting Enzyme 2 (ACE2) receptor.</p>

Molecular Basis of Iterative C–H Oxidation by TamI, a Multifunctional P450 Monooxygenase from the Tirandamycin Biosynthetic Pathway

2020 ◽  
Author(s):  
Sean A. Newmister ◽  
Kinshuk Raj Srivastava ◽  
Rosa V. Espinoza ◽  
Kersti Caddell Haatveit ◽  
Yogan Khatri ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Molecular Basis ◽  
Hydrophobic Interactions ◽  
Cytochromes P450 ◽  
Targeted Mutagenesis ◽  
P450 Monooxygenase ◽  
Bond Functionalization ◽  
Dynamics Simulations

Biocatalysis offers an expanding and powerful strategy to construct and diversify complex molecules by C-H bond functionalization. Due to their high selectivity, enzymes have become an essential tool for C-H bond functionalization and offer complementary reactivity to small-molecule catalysts. Hemoproteins, particularly cytochromes P450, have proven effective for selective oxidation of unactivated C-H bonds. Previously, we reported the in vitro characterization of an oxidative tailoring cascade in which TamI, a multifunctional P450 functions co-dependently with the TamL flavoprotein to catalyze regio- and stereoselective hydroxylations and epoxidation to yield tirandamycin A and tirandamycin B. TamI follows a defined order including 1) C10 hydroxylation, 2) C11/C12 epoxidation, and 3) C18 hydroxylation. Here we present a structural, biochemical, and computational investigation of TamI to understand the molecular basis of its substrate binding, diverse reactivity, and specific reaction sequence. The crystal structure of TamI in complex with tirandamycin C together with molecular dynamics simulations and targeted mutagenesis suggest that hydrophobic interactions with the polyene chain of its natural substrate are critical for molecular recognition. QM/MM calculations and molecular dynamics simulations of TamI with variant substrates provided detailed information on the molecular basis of sequential reactivity, and pattern of regio- and stereo-selectivity in catalyzing the three-step oxidative cascade.<br>

scholarly journals Sweet taste of heavy water

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Natalie Ben Abu ◽  
Philip E. Mason ◽  
Hadar Klein ◽  
Nitzan Dubovski ◽  
Yaron Ben Shoshan-Galeczki ◽  
...  
Keyword(s):  
Heavy Water ◽  
Calcium Release ◽  
Homology Modelling ◽  
Taste Receptor ◽  
Chemical Properties ◽  
Sweet Taste ◽  
Minor Effect ◽  
Dynamics Simulations ◽  
A Minor ◽  
Physical And Chemical

AbstractHydrogen to deuterium isotopic substitution has only a minor effect on physical and chemical properties of water and, as such, is not supposed to influence its neutral taste. Here we conclusively demonstrate that humans are, nevertheless, able to distinguish D2O from H2O by taste. Indeed, highly purified heavy water has a distinctly sweeter taste than same-purity normal water and can add to perceived sweetness of sweeteners. In contrast, mice do not prefer D2O over H2O, indicating that they are not likely to perceive heavy water as sweet. HEK 293T cells transfected with the TAS1R2/TAS1R3 heterodimer and chimeric G-proteins are activated by D2O but not by H2O. Lactisole, which is a known sweetness inhibitor acting via the TAS1R3 monomer of the TAS1R2/TAS1R3, suppresses the sweetness of D2O in human sensory tests, as well as the calcium release elicited by D2O in sweet taste receptor-expressing cells. The present multifaceted experimental study, complemented by homology modelling and molecular dynamics simulations, resolves a long-standing controversy about the taste of heavy water, shows that its sweet taste is mediated by the human TAS1R2/TAS1R3 taste receptor, and opens way to future studies of the detailed mechanism of action.

scholarly journals Physicochemical Characteristics of Arginine Enriched NaF Varnish: An In Vitro Study

Polymers ◽  
2020 ◽  
Vol 12 (12) ◽  
pp. 2998
Author(s):  
Mohammed Nadeem Bijle ◽  
Manikandan Ekambaram ◽  
Edward Lo ◽  
Cynthia Yiu
Keyword(s):  
Molecular Dynamics ◽  
Physical Properties ◽  
Artificial Saliva ◽  
Chemical Properties ◽  
In Vitro Study ◽  
Physicochemical Characteristics ◽  
Vitro Study ◽  
Physical And Chemical ◽  
Stable Matrix

The in vitro study objectives were to investigate the effect of arginine (Arg) incorporation in a 5% sodium fluoride (NaF) varnish on its physical and chemical properties including F/Arg release. Six experimental formulations were prepared with L-arginine (L-Arg) and L-arginine monohydrochloride at 2%, 4%, and 8% w/v in a 5% NaF varnish, which served as a control. The varnishes were subjected to assessments for adhesion, viscosity, and NaF extraction. Molecular dynamics were simulated to identify post-dynamics total energy for NaF=Arg/Arg>NaF/Arg<NaF concentrations. The Arg/F varnish release profiles were determined in polyacrylic lactate buffer (pH-4.5; 7 days) and artificial saliva (pH-7; 1 h, 24 h, and 12 weeks). Incorporation of L-Arg in NaF varnish significantly influences physical properties ameliorating retention (p < 0.001). L-Arg in NaF varnish institutes the Arg-F complex. Molecular dynamics suggests that NaF>Arg concentration denotes the stabilized environment compared to NaF<Arg (p < 0.001). The 2% Arg-NaF exhibits periodic perennial Arg/F release and shows significantly higher integrated mean F release than NaF (p < 0.001). Incorporating 2% L-arginine in 5% NaF varnish improves its physical properties and renders a stable matrix with enduring higher F/Arg release than control.

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