scholarly journals The Conformation and Assignment of the Proton NMR Spectrum in Water of DX600, a Bioactive Peptide with a Random Coil Conformation

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Wayne E. Steinmetz ◽  
Timothy N. Carrell ◽  
Richard B. Peprah
Keyword(s):  
Molecular Dynamics ◽  
Selective Inhibitor ◽  
Random Coil ◽  
Proton Spectrum ◽  
Converting Enzyme ◽  
Small Peptide ◽  
Nmr Spectrum ◽  
Angiotensin Converting Enzyme 2 ◽  
Nmr Methods ◽  
Dynamics Simulations

DX600, a small peptide with 26 residues, is a potent, highly selective inhibitor of angiotensin converting enzyme 2 (ACE2). A range of NMR methods including TOCSY and ROESY yield an assignment of its proton spectrum in water and constraints on its conformation. Constrained molecular dynamics simulations of solvated DX600 show that the peptide's most abundant conformer adopts a predominantly random coil conformation. Constrained by the disulfide bond, its backbone defines an overhand knot with frayed ends.

scholarly journals Computational design of ACE2-based short peptide inhibitors of SARS-CoV-2

2020 ◽  
Author(s):  
Yanxiao Han ◽  
Petr Kral
Keyword(s):  
Molecular Dynamics ◽  
Computational Design ◽  
Peptide Inhibitors ◽  
Converting Enzyme ◽  
Protease Domain ◽  
Alpha Helices ◽  
Angiotensin Converting Enzyme 2 ◽  
Short Peptide ◽  
Binding Domains ◽  
Dynamics Simulations

<div>Peptide inhibitors against the SARS-CoV-2 coronavirus, currently causing a worldwide pandemic, are designed and simulated. The inhibitors are formed by two sequential self-supporting alpha-helices (bundle) extracted from the protease domain (PD) of angiotensin-converting enzyme 2 (ACE2), which binds to the SARS-CoV-2 receptor binding domains. Molecular dynamics simulations revealed that the peptides maintain their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2, determined by their sequences and conformations. The proposed peptide inhibitors could provide simple therapeutics against the COVID-19 disease.</div>

scholarly journals Computational design of ACE2-based short peptide inhibitors of SARS-CoV-2

2020 ◽  
Author(s):  
Yanxiao Han ◽  
Petr Kral
Keyword(s):  
Molecular Dynamics ◽  
Computational Design ◽  
Peptide Inhibitors ◽  
Converting Enzyme ◽  
Protease Domain ◽  
Alpha Helices ◽  
Angiotensin Converting Enzyme 2 ◽  
Short Peptide ◽  
Binding Domains ◽  
Dynamics Simulations

<div>Peptide inhibitors against the SARS-CoV-2 coronavirus, currently causing a worldwide pandemic, are designed and simulated. The inhibitors are formed by two sequential self-supporting alpha-helices (bundle) extracted from the protease domain (PD) of angiotensin-converting enzyme 2 (ACE2), which binds to the SARS-CoV-2 receptor binding domains. Molecular dynamics simulations revealed that the peptides maintain their secondary structure and provide a highly specific and stable binding (blocking) to SARS-CoV-2, determined by their sequences and conformations. The proposed peptide inhibitors could provide simple therapeutics against the COVID-19 disease.</div>

scholarly journals Computational analysis on the ACE2-derived peptides for neutralizing the ACE2 binding to the spike protein of SARS-CoV-2

2020 ◽  
Author(s):  
Cecylia S. Lupala ◽  
Vikash Kumar ◽  
Xuanxuan Li ◽  
Xiao-dong Su ◽  
Haiguang Liu
Keyword(s):  
Molecular Dynamics ◽  
Severe Acute Respiratory Syndrome ◽  
Angiotensin Converting Enzyme ◽  
Computational Analysis ◽  
Spike Protein ◽  
Short Peptides ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Dynamics Simulations

ABSTRACTThe severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of the COVID-19, is spreading globally and has infected more than 3 million people. It has been discovered that SARS-CoV-2 initiates the entry into cells by binding to human angiotensin-converting enzyme 2 (hACE2) through the receptor binding domain (RBD) of its spike glycoprotein. Hence, drugs that can interfere the SARS-CoV-2-RBD binding to hACE2 potentially can inhibit SARS-CoV-2 from entering human cells. Here, based on the N-terminal helix α1 of human ACE2, we designed nine short peptides that have potential to inhibit SARS-CoV-2 binding. Molecular dynamics simulations of peptides in the their free and SARS-CoV-2 RBD-bound forms allow us to identify fragments that are stable in water and have strong binding affinity to the SARS-CoV-2 spike proteins. The important interactions between peptides and RBD are highlighted to provide guidance for the design of peptidomimetics against the SARS-CoV-2.

scholarly journals Molecular Dynamics Simulation Study of the Interaction between Human Angiotensin Converting Enzyme 2 and Spike Protein Receptor Binding Domain of the SARS-CoV-2 B.1.617 Variant

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1244
Author(s):  
Priya Antony ◽  
Ranjit Vijayan
Keyword(s):  
Molecular Dynamics ◽  
Angiotensin Converting Enzyme ◽  
Molecular Dynamics Simulations ◽  
Receptor Binding ◽  
Binding Domain ◽  
Receptor Binding Domain ◽  
Converting Enzyme ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Dynamics Simulations

The COVID-19 pandemic, caused by the SARS-CoV-2 virus, has had a significant impact on people’s daily lives. The rapidly spreading B.1.617 lineage harbors two key mutations—L452R and E484Q—in the receptor binding domain (RBD) of its spike (S) protein. To understand the impact and structural dynamics of the variations in the interface of S protein and its host factor, the human angiotensin-converting enzyme 2 (hACE2), triplicate 500 ns molecular dynamics simulations were performed using single (E484Q or L452R) and double (E484Q + L452R) mutant structures and compared to wild type simulations. Our results indicate that the E484Q mutation disrupts the conserved salt bridge formed between Lys31 of hACE2 and Glu484 of S protein. Additionally, E484Q, which could favor the up conformation of the RBD, may help in enhanced hACE2 binding and immune escape. L452R introduces a charged patch near the binding surface that permits increased electrostatic attraction between the proteins. An improved network of intramolecular interactions observed is likely to increase the stability of the S protein and conformational changes may prevent the binding of neutralizing antibodies. The results obtained from the molecular dynamics simulations suggest that structural and dynamic changes introduced by these variations enhance the affinity of the viral S protein to hACE2 and could form the basis for further studies.

scholarly journals ACE2 fragment as a decoy for novel SARS-Cov-2 virus

2020 ◽  
Author(s):  
Fabiana Renzi ◽  
Dario Ghersi
Keyword(s):  
Molecular Dynamics ◽  
Angiotensin Converting Enzyme ◽  
Molecular Dynamics Simulations ◽  
Cellular Membrane ◽  
Converting Enzyme ◽  
S Protein ◽  
Angiotensin Converting Enzyme 2 ◽  
Viral Binding ◽  
Binding Surface ◽  
Dynamics Simulations

Novel SARS-Cov-2 enters human cells via interaction between the surface spike (S) glycoprotein and the cellular membrane receptor angiotensin-converting enzyme 2 (ACE2). Using a combination of comparative structural analyses of the binding surface of the S protein to ACE2, docking experiments, and molecular dynamics simulations we computationally identified a minimal, stable fragment of ACE2. This fragment binds to the S protein, is soluble, and appears not to bind to the physiological ligand angiotensinII. These results suggest a possible use of the ACE2 fragment as a decoy that could interfere with viral binding by competition.

scholarly journals IDENTIFICATION OF POTENTIAL SALMONELLA TYPHI BETA-LACTAMASE TEM 1 INHIBITORS USING PEPTIDOMIMETICS, VIRTUAL SCREENING, AND MOLECULAR DYNAMICS SIMULATIONS

2018 ◽  
Vol 10 (1) ◽  
pp. 91
Author(s):  
Rakesh K. R. Pandit ◽  
Dinesh Gupta ◽  
Tapan K. Mukherjee
Keyword(s):  
Molecular Dynamics ◽  
Antibiotic Resistance ◽  
Virtual Screening ◽  
Molecular Dynamics Simulations ◽  
Active Site ◽  
Beta Lactamase ◽  
Ramachandran Plot ◽  
Small Peptide ◽  
In Silico Docking ◽  
Dynamics Simulations

Objective: The purpose of this study was to identify a potential peptidomimetic S. typhi Beta-lactamase TEM 1 inhibitor to tackle the antibiotic resistance among S. typhi.Methods: The potential peptidomimetic inhibitor was identified by in silico docking of the small peptide WFRKQLKW with S. typhi Beta-lactamase TEM 1. The 3D coordinate geometry of the residues of small peptide interacting with the active site of the receptor was generated and mimics were identified using PEP: MMs: MIMIC server. All the identified mimics were docked at the active site of the receptor using Autodock 4.2 and the best-docked complex was selected on the basis of binding energy and number of H-bonds. The complex was then subjected to molecular dynamics simulations of 30 ns using AMBER 12 software package. The stereochemical stability of the Beta-lactamase TEM 1-WFRKQLKW complex was estimated with the help of Ramachandran plot using PROCHECK tool.Results: In the present study, a new potential peptidomimetic inhibitor (ZINC05839264) of Beta-lactamase TEM 1 has been identified based on antimicrobial peptide WFRKQLKW by virtual screening of the MMsINC database. The docking and molecular simulation studies revealed that the mimic binds more tightly to the active site of the receptor than the peptide. The Ramachandran plot also shows that the Beta-lactamase TEM 1-mimic complex is stereo chemically more stable than Beta-lactamase TEM 1-WFRKQLKW complex as more number of residues (93.6%) are falling under the core region of the plot in case of the former.Conclusion: The study shows that the peptidomimetic compound can act as a potential inhibitor of S. typhi Beta-lactamase TEM 1 and further it can be developed into more effective therapeutic to tackle the problem of antibiotic resistance.

An evaluation of high resolution nuclear magnetic resonance experiments and protocols in the structure elucidation of organic molecules. I. A relatively simple system, brucine

1985 ◽  
Vol 63 (2) ◽  
pp. 483-490 ◽  
Author(s):  
Michael A. Bernstein ◽  
Laurance D. Hall
Keyword(s):  
High Resolution ◽  
Chemical Shift ◽  
Structural Information ◽  
Nuclear Overhauser Effect ◽  
Proton Spectrum ◽  
Nmr Spectrum ◽  
H Nmr ◽  
Overhauser Effect ◽  
Nuclear Overhauser ◽  
Nmr Methods

Using a combination of one-dimensional (1D) and two-dimensional (2D) high resolution nmr methods, the 1H nmr spectrum of brucine was fully assigned. The 2D J-resolved and homonuclear chemical shift correlated (COSY) experiments provided assignments without full structural information; this was obtained from nuclear Overhauser effect (nOe) enhancement experiments (1D and 2D). With the proton spectrum fully assigned, proton-bearing carbons in the 13C nmr spectrum were easily assigned using the 2D heteronuclear chemical shift correlation map (CSCM) experiment.

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