Insights from in silico study of receptor energetics of SARS-CoV-2 variants.

The emergence of new variants of the novel coronavirus SARS-CoV-2 with increased infectivity, superior virulence, high transmissibility, and unmatched immune escape has demonstrated the adaptability and evolutionary fitness of the virus. The subject of relative order of the binding affinity of SARS-CoV-2 variants with the human ACE2 (hACE2) receptor is hotly debated and its resolution has implications for drug design and development. In this work, we have investigated the energetics of the binding of receptor binding domain (RBD) of SARS-CoV-2 variants of concern (VOCs): Beta (B.1.351), Delta (B.1.617.2), Omicron (B.1.1.529), variant of interest (VOI): Kappa (B.1.617.1), and Delta Plus (B.1.617.2.1) variant with the human ACE2 receptor by using the umbrella sampling (US) method. Our work indicates that Delta and Delta Plus variants have greater values of the US binding free energy than Wild-type (WT), whereas Beta, Kappa, and Omicron variants have lower values. Further analysis of hydrogen bonding, salt bridges, non-bonded interaction energy, and contact surface area at the RBD-hACE2 interface establish Delta as the variant with the highest binding affinity among these variants.

Base flipping mechanism and binding strength of methyl-damaged DNA during the interaction with AGT.

Methyl damage to DNA bases is common in the cell nucleus. O6-alkylguanine-DNA alkyl transferase (AGT) may be a promising candidate for direct damage reversal in methylated DNA (mDNA) at the O6 point of the guanine. Indeed, atomic-level investigations in the contact region of AGT-DNA complex can provide an in-depth understanding of their binding mechanism, allowing to evaluate the silico-drug nature of AGT and its utility in removing methyl damage in DNA. In this study, molecular dynamics (MD) simulation was utilized to examine the flipping of methylated nucleotide, the binding mechanism between mDNA and AGT, and the comparison of binding strength prior and post methyl transfer to AGT. The study reveals that methylation at the O6 atom of guanine weakens the hydrogen bond (H-bond) between guanine and cytosine, permitting for the flipping of such nucleotide. The formation of a H-bond between the base pair of methylated nucleotide (i.e., cytosine) and the intercalated arginine of AGT also forces the nucleotide to rotate. Following that, electrostatics and van der Waals contacts as well as hydrogen bonding contribute to form the complex of DNA and protein. The stronger binding of AGT with DNA before methyl transfer creates the suitable condition to transfer methyl adduct from DNA to AGT.

Structural stability of R-state conformation of carbonmonoxyl sickle and normal hemoglobin dimer.

A mutation at the sixth residue, glutamic acid to valine, in beta chain of hemoglobin distorts the entire shape of hemoglobin into a sickle shape. The investigation of the binding mechanisms of different chains of hemoglobin under the mutated condition can give an understanding of the molecular distortion. In this work, we have studied the binding mechanism between two chains in the dimer structure of the R-state conformation of carbonmonoxyl sickle hemoglobin and is compared with that of normal hemoglobin by using molecular dynamics simulations. The binding strength between α-chain (PROA) and ß-chain (PROB) in hemoglobin dimer has been analyzed by estimating hydrogen bonds, salt bridges, hydrophobic interactions and non-bonded interactions (electrostatics and van der Waals). The quantitative estimation of aforementioned interactions depicts that the structural stability of normal hemoglobin dimer is found to be greater than that of sickle one. The outcomes of such interactions are also supported by the estimated free energy between the chains in R-state conformation of the dimers. The difference of binding free energy, calculated by utilizing the umbrella sampling technique, is found to be ≈ (0.67 ± 0.06) kcal/mol.Communicated by Ramaswamy H. Sarma.

Adsorption of water on C sites vacancy defected graphene/h-BN: First-principles study.

Heterostructures (HS), vacancy defects in HS, and molecular adsorption on defected HS of 2D materials are fervently inspected for a profusion of applications because of their aptness to form stacked layers that confer approach to an amalgamation of favorable electronic and magnetic properties. In this context, graphene (Gr), hexagonal boron nitride (h-BN), HS of graphene/h-BN (Gr/h-BN), and molecular adsorption on Gr/h-BN offer promising prospects for electronic, spintonic, and optoelectronic devices. In this study, we investigated the structural, electronic, and magnetic properties of C sites vacancy defects in Gr/h-BN HS and adsorption of water molecule on defected Gr/h-BN HS materials by using first-principles calculations based on spin-polarized density functional theory method within van der Waals (vdW) corrections DFT-D2 approach. We found that these considered materials are stable 2D vdW HS. Based on band structure calculations, they are semimetallic, and on density of states and partial density of states analysis, they are magnetic materials. The magnetic moment developed in these defected systems is due to the unpaired up-spin and down-spin states in the orbitals of atoms present in the materials created by the vacancy defects.

First-principles study of structure, electronic, and magnetic properties of C sites vacancy defects in water adsorbed graphene/MoS2 van der Waals heterostructures.

We have studied structure, electronic, and magnetic properties of water adsorbed vdW heterostructure graphene/MoS2 (w-(HS)G/MoS2) and its C sites vacancy defects materials (w-Catoms-vacancy-(HS)G/MoS2) by using a spin polarized density functional theory (DFT) method of calculations within DFT-D2 approach to take in to account of vdW interactions. All the structures are optimized and relaxed by BFGS method using computational tool Quantum ESPRESSO package. By structural analysis, we found that both w-(HS)G/MoS2 and w-Catoms-vacancy-(HS)G/MoS2 are stable materials. The stability and compactness of these materials decrease with an increase in their defects concentrations. From band structure calculations, our findings show that w-(HS)G/MoS2 has a metallic nature, and there is formation of n-type Schottky contact of barrier height 0.42 eV. Also, the left 1C atom vacancy defects in w-(HS)G/MoS2 (L1C-w-(HS)G/MoS2) and center 1C atom vacancy defects in w-(HS)G/MoS2 (C1C-w-(HS)G/MoS2) materials have no band gap for up and down spin electronic states, indicating that they have also a metallic nature. On the other hand, 2C atom vacancy defects in w-(HS)G/MoS2 (2C-w-(HS)G/MoS2) has a small band gap for up spins states and no band gap for down spin electronic states which means that the band structure resembles with half metallic nature. Thus, the endowment of metallic nature decreased with increase in the concentrations of defects in structures. To study the magnetic properties in materials, DOS and PDOS calculations are used, and we found that non-magnetic w-(HS)G/MoS2 material changes to magnetic in all the three different L1C-w-(HS)G/MoS2, C1C-w-(HS)G/MoS2, and 2C-w-(HS)G/MoS2 materials with vacancy. L1C-w-(HS)G/MoS2, C1C-w-(HS)G/MoS2, and 2C-w-(HS)G/MoS2 have magnetic moments of + 0.21 µB/cell, + 0.26 µB/cell, and - 2.00 µB/cell, respectively. The spins of electrons in 2s and 2p orbitals of C atoms give a principal effect of magnetism in w-Catoms-vacancy-(HS)G/MoS2 materials.

Study of structural and transport properties of argon, krypton, and their binary mixtures at different temperatures.

Molecular dynamics simulation of argon, krypton, and their binary mixtures were performed at different temperatures and constant pressure (P = 1.013 bar) using GROMACS - Groningen Machine for Chemical Simulations. The gases are modeled by Lennard-Jones pair potential, with parameters taken from the literature. The study of radial distribution functions (RDFs) shows a single peak which indicates that there is no packing effect in gaseous state for argon, krypton, and their binary mixtures. The self-diffusion coefficients of argon and krypton is determined by using mean-square displacement(MSD) method and the mutual diffusion coefficients of binary mixtures are determined using Darken's relation. The values of simulated diffusion coefficients are compared with their corresponding theoretical values, numerical estimation, and experimental data. A good agreement between these sets of data is found. The diffusion coefficients obey Arrhenius behavior to a good extent for both pure components and binary mixtures. The values of simulated diffusion coefficient are used to estimate viscosities and thermal conductivities which agree with theoretical values, numerical estimation, and experimental data within 10 %. These results support that the LJ potential is sufficient for description of molecular interactions in argon and krypton.

A study of magnetism in disordered Pt-Mn, Pd-Mn and Ni-Mn alloys: an augmented space recursion approach.

In this paper we shall study three binary alloy systems, one constituent of which is Mn. The other constituents are chosen from a particular column of the periodic table: Ni(3d), Pt (4d) and Pd (5d). As we go down the column, the d-bands become wider, discouraging spin-polarization. In a disordered alloy, the situation becomes more complicated, as the exchange interaction between two atoms is environment dependent. We shall compare and contrast their magnetic behaviour using robust electronic structure techniques. In all three alloy systems conjectures are made to explain experimental data. In this paper we shall examine whether there is any basis to these conjectures.