Riding the Wave: Unveiling the Conformational Waves from RBD of SARS-CoV‑2 Spike Protein to ACE2

The binding affinity between angiotensin-converting enzyme 2 (ACE2) and the receptor-binding domain (RBD) plays a crucial role in the transmission and reinfection of SARS-CoV2. Here, microsecond molecular dynamics simulations revealed that point mutations in the RBD domain induced conformational transitions that determined the binding affinity between ACE2 and RBD. These structural changes propagated through the RBD domain, altering the orientation of both ACE2 and RBD residues at the binding site. ACE2 receptor shows significant structural heterogeneity, whereas its binding to the RBD domain indicates a much greater degree of structural homogeneity. The receptor was more flexible in its unbound state with the binding of RBD domains inducing structural transitions. The structural heterogeneity observed in the ACE2 unbound form plays a role in the promiscuity of viral entry, as it may allow the receptor to interact with various related and unrelated ligands. Furthermore, rigidity may be important for stabilizing the complex and ensuring the proper orientation of the RBD-binding interface with ACE2. The greater structural homogeneity observed in the ACE2-RBD complex revealed the effectiveness of neutralizing antibodies and vaccines that are primarily directed toward the RBD-binding interface. The binding of the B38 monoclonal antibody revealed restricted conformational transitions in the RBD and ACE2 receptors, attributed to its potent binding interaction

Supplementary Material.pdf

<p><b><u>Supplementary Information</u></b></p> <p><b>Structure, Stability and water permeation of ([D-Leu-L-Lys-(D-Gln-L-Ala)₃]) cyclic peptide nanotube: A molecular dynamics study</b></p> <p>Nikhil Maroli¹, Ponmalai Kolandaivel^2*</p> <p>1. Computational Biology Division,DRDO BU CLS,Coimbatore-641046,Tamil Nadu,INDIA</p> <p>2.Department of Physics, Bharathiar University, Coimbatore, Tamil Nadu, INDIA</p> <p> </p> <p>*Corresponding author:</p> <p>E-mail address: [email protected]</p><p><br></p><p>https://doi.org/10.1080/08927022.2017.1366653<br></p

Structure, stability and water permeation of ([D-Leu-L-Lys-(D-Gln-L-Ala)₃]) cyclic peptide nanotube: a molecular dynamics study

<p>The structural stability of 8 × ([D-Leu-L-Lys-(D-Gln-L-Ala)₃]) cyclic peptide nanotube (CPN) in water and different phospholipid bilayers were explored by 100 ns independent molecular dynamics (MD) simulations. The role of non-bonded interaction energy between the side and main chains of cyclic peptide rings in different membrane environments assessed, wherein the repulsive electrostatic interaction energy between neighbouring cyclic peptide rings was found adequate to break hydrogen bond energy thereby to crumple CPN. Further, the water permeation across the CPN channel was studied in four types of phospholipid bilayers- DMPG (1,2-Dimyristoyl-sn-glycero-3-phosphorylglycerol), DMPS (1,2-Dimyristoyl-sn-glycero-3-phosphoserine), POPC (1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine) and POPE (1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine) from MD simulations. DMPS membrane shows higher non-bonded interaction energies (−1913.06 kJ/mol of electrostatic interaction energy and −994.13 kJ/mol of van der Waals interaction energy) with CPN due to the presence of polar molecules in lipid structure. Thusly, the non-bonded interaction energies were essential towards the stability of CPN than hydrogen bonds between the nearby cyclic peptides. The result also reveals the role of side chains, hydrogen bonds and non-bonded interaction energies in an aqueous environment. The diffusion coefficient of water obtained from means square deviation calculation shows similar coefficients irrespective of the lipid surroundings. However, the permeation coefficients demonstrate water flow in the channel relies upon the environment.</p

The Potential role of Procyanidin as a Therapeutic Agent against SARS-CoV-2: A Text Mining, Molecular Docking and Molecular Dynamics Simulation Approach

A novel coronavirus (SARS-CoV-2) has caused a major outbreak in human all over the world. There are several proteins interplay during the entry and replication of this virus in human. Here, we have used text mining and named entity recognition method to identify co-occurrence of the important COVID 19 genes/proteins in the interaction network based on the frequency of the interaction. Network analysis revealed a set of genes/proteins, highly dense genes/protein clusters and sub-networks of Angiotensin-converting enzyme 2 (ACE2), Helicase, spike (S) protein (trimeric), membrane (M) protein, envelop (E) protein, and the nucleocapsid (N) protein. The isolated proteins are screened against procyanidin-a flavonoid from plants using molecular docking. Further, molecular dynamics simulation of critical proteins such as ACE2, Mpro and spike proteins are performed to elucidate the inhibition mechanism. The strong network of hydrogen bonds and hydrophobic interactions along with van der Waals interactions inhibit receptors, which are essential to the entry and replication of the SARS-CoV-2. The binding energy which largely arises from van der Waals interactions is calculated (ACE2=-50.21 ± 6.3, Mpro=-89.50 ± 6.32 and spike=-23.06 ± 4.39) through molecular mechanics Poisson-Boltzmann surface area also confirm the affinity of procyanidin towards the critical receptors.</p

Scalable Pillar[5]arene-Integrated Poly(arylate-amide) Molecular Sieve Membranes to Separate Light Gases

Molecular sieve membranes and their analogues could potentially transform energy-intensive gas separation processes. However, many such membranes suffer from either limited process ability or physical stability including plasticization of semi-flexible microstructures. Here, we report on a new variation of all-polymer-based molecular sieve membranes that could tackle these specific challenges. These membranes were prepared by the interfacial polymerization of pillar[5]arene, m-phenylenediamine, and trimesoyl chloride to create characteristic poly(arylate-amide) heteropolymer microstructures. Pillar[S]arenes were crosslinked into the films with net weight fractions of up to similar to 47%, wherein the, 4.7 angstrom cavities of pillar[5]arenes were interconnected with similar to 2.8 angstrom apertures. These microstructures provided preferred permeation paths for smaller molecules (He and H-2) among the tested light gases (He, H-2, CO2, O-2, N-2, and CH4) and resulted in significant molecular sieving effects with representative pure gas selectivities of 32 (H-2/CO2), 150 (CO2/CH4), 4600 (H-2/CH4), 13 (O-2/N-2), and 4.7 (N-2/CH4) at 35 degrees C and 10 atm. These separation factors outperform most polymer-based gas separation membranes, while providing membrane features such as thin film barriers, cross-linked polymer backbones, and excellent processability resulting from interfacial polymerization that are critical for large-scale operations.11Nsciescopu