Journal of Computational Biophysics and Chemistry

SARS-CoV-2 entrance to the host cells is started by the interaction between receptor binding domain (RBD) of the spike (S) protein on the virus with the angiotensin-converting enzyme 2 (ACE2) receptor which is very important in the onset of viral infection. Interference with this interaction can be a promising way to prevent Covid-19 infection. In this study, a novel potential therapeutic peptide was designed in silico based on the key interacting amino acids of ACE2 against SARS-CoV-2 S protein. In our computational analysis, a peptide consisting of residues 19–48 of ACE2 was chosen as the wild-type peptide. Based on this peptide, six mutant peptides (Mu_P1-6) were designed and then assessed in term of interaction with S protein. The result of protein-peptide docking by HADDOCK web server and then immunological analysis by SVMTriP epitope prediction tool leads to choose Mu_P3 as the best mutant. Molecular dynamics simulations of wild-type peptide-S protein complex and Mu_P3-S protein complex, showed Mu_P3 has better interaction with S protein than wild type peptide (interaction energies $-897.14$ vs. $-784.13$ (kJ/mol)) which can be a potential therapeutic peptide for Covid-19 pandemic.

Graphitic carbon nitride ($g$-C₃N₄) is the most efficient nanocarrier which is used in the delivery of many drugs. In this study, $g$-C₃N₄ was used as a carrier for flutamide (anticancer drug) loading, and its effectiveness as a drug-delivery carrier for flutamide drug is explored. At ground and excited states, various calculations including noncovalent-interaction analysis (NCI) charge-decomposition analysis (CDA), electron localization function (ELF) analysis, Nonbonding-orbital analysis (NBO), dipole moment and bandgap of $g$-C₃N₄, flutamide drug and $g$-C₃N₄-flutamide complex ($g$-C₃N₄-FLUT complex) were performed. The nitrogen atom of $g$-C₃N₄ makes a weak van der Waals interaction with the oxygen and fluorine of flutamide anticancer drug, and these interactions were further illustrated by the NCI graph. These weak van der Waals interactions are helpful in drug-offloading from $g$-C₃N₄ at its targeted-spot. The investigation of highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) demonstrated that the charge was transferred from $g$-C₃N₄ to flutamide drug. To further understand the phenomena of charge-transfer in the $g$-C₃N₄-FLUT complex, CDA analysis was performed. The calculated ${\lambda }_{max}$ of excited states of $g$-C₃N₄-FLUT was blue-shifted by 25nm. The Photoinduced Electron Transfer (PET) process was fully described by the electron-hole theory, which demonstrated that the fluorescence-quenching may occur. Overall, it can be stated that the $g$-C₃N₄ is a promising nanocarrier for use in drug delivery among other nanocarriers owing to their higher drug loading capability and low cytotoxicity.

Hydrogen is considered as one of the attractive environmentally friendly materials with zero carbon emission. Hydrogen storage is still challenging for its use in various energy applications. That’s why hydrogen gained more and more attention to become a major fuel of today’s energy consumption. Therefore, nowadays, hydrogen storage materials are under extensive research. Herein, efforts are being devoted to design efficient systems which could be used for future hydrogen storage purposes. To this end, we have employed density functional theory (DFT) to optimize the geometries of the designed inorganic Al${}_{12}$N${}_{12}$ nanoclusters with transition metals (Fe, Co, Ni, Cu and Zn). Various positions of metal encapsulated Al${}_{12}$N${}_{12}$ are examined for efficient hydrogen adsorption. After adsorption of H₂ on late transition metals encapsulated Al${}_{12}$N${}_{12}$ nanocluster, different geometric parameters like frontier molecular orbitals, adsorption energies and nature bonding orbitals have been performed for exploring the potential of metal encapsulated for hydrogen adsorption. Moreover, molecular electrostatic potential (MEP) analysis was also performed in order to explore the different charge separation upon H₂ adsorption on metals encapsulated Al${}_{12}$N${}_{12}$ nanoclusters. Also, global indices of reactivity like ionization potential, electron affinity, electrophilic index, chemical softness and chemical hardness were also examined by using DFT. The adsorption energy results suggested encapsulation of late transition metals in Al${}_{12}$N${}_{12}$ nanocage efficiently enhancing the adsorption capability of Al${}_{12}$N${}_{12}$ for hydrogen adsorption. Results of all analysis suggested that our designed systems are efficient candidates for hydrogen adsorption. Thus, we recommended a novel kind of systems for hydrogen storage materials.

Non-Structural Protein 16 (NSP-16) is one of the most suitable targets for discovery of drugs for corona viruses including SARS-CoV-2. In this study, drug discovery of SARS-CoV-2 nsp-16 has been accomplished by pharmacophore-based virtual screening among some analogs (FDA approved drugs) and marine natural plants (MNP). The comparison of the binding energies and the inhibition constants was determined using molecular docking method. Three compounds including two FDA approved (Ibrutinib, Idelalisib) and one MNP (Kumusine) were selected for further investigation using the molecular dynamics simulations. The results indicated that Ibrutinib and Idelalisib are oral medications while Kumusine, with proper hydrophilic and solubility properties, is an appropriate candidate for nsp-16 inhibitor and can be effective to control COVID-19 disease.

Migraine is a re-occurring type of headache and causes moderate-to-severe pain that is troubling or pulsing. The pain occurs in half of the head, and common symptoms are photophobia, phonophobia, nausea, depression, anxiety, vomiting, etc. This study evaluates the prevalence of migraine and responsible genes through molecular modeling in the region of Bahawalpur, Pakistan. This research was aimed to determine the prevalence of migraine-causing genes in the population of Bahawalpur and also to do molecular and in-silico analysis of migraine-causing gene as no similar research was conducted before. The disease was characterized and diagnosed under the criteria of the Second Edition of the International Classification of Headache Disorders and molecular identification of migraine-causing genes, i.e. GRIA1, GRIA3, and ESR1, by PCR amplification. The total number of samples collected for migraine patients was 230, out of which 30 were positive for PCR amplification of the genes GRIA1, GRIA3, and ESR1. Therapeutic potentials of commercial drugs, namely Cyclobenzaprine, Divalproex, Ergotamine, and Sumatriptan, were analyzed in silico through molecular docking. Ergotamine demonstrated the highest binding affinity of $-$8.4 kcal/mol for the target molecule and, hence, the highest potential. The bivariate analysis showed that the prevalence of migraine concerning gender and age was significantly correlated ($\alpha =0.01$, $p=0.212$). It was observed that almost 31.4% of women suffered from headaches daily, 70% weekly, 28.1% monthly, and 23.5% rarely. Comparatively, only 8.3% of males suffered from daily headaches, 34% weekly, 12.8% monthly, and 14.9% rarely. The study shows promising results and encourages future researchers to conduct such a comprehensive epidemiological study on an even larger population to justify a more precise association of risk factors involved in migraine pathophysiology.

Coronavirus Acute Respiratory Syndrome (SARS-CoV-2) is a very recent viral infection and has generated one of the world’s biggest problems of all time. There is no scientific evidence and clinical trials to indicate that possible therapies have shown results in suspected or confirmed patients other than the use of immunizations. Given the above, some substances are being studied to be applied to contain their spread and further damage. This work aims to perform an in silico study of amoxicillin, widely known as an antibiotic and used to prevent bacterial infections and a possible biomarker made from a complex with Europium (Eu). It was shown to have the ability to interact with the COVID-19 protein in M^pro protease as ligands. The study was conducted using the AutoDock Vina with Lamarckian genetic model algorithm (GA) combined with the estimation of grid-based energy in rigid and flexible conformation. Compared to affinity energy, amoxicillin presented $-7.7$kcal/mol, which was better than its co-crystallized ligand in the study. The Europium complex, where its synthesis was also demonstrated in this work, presented energy of $-6.3$kcal/mol with hydrogen bonds and possible color change when UV light was applied. For the choice of the best poses in the simulation, the neural network parameter, NNScore2, was used. It can be affirmed that this study is still introductory but promising both in the treatment and identification of the virus.

It has been a great challenge for scientists to develop an anti-Covid drug/vaccine with fewer side effects, since the coronavirus pandemic began. Of course, the prescription of chiral drugs (chloroquine or hydroxychloroquine) has been proved wrong because these chiral drugs neither kill the virus nor eliminate it from the body, but block SARS-CoV-2 from binding to human cells. Another hurdle facing the world is not only the positive test of the patient recovered from coronavirus, but also the second wave of Covid-19. Hence, the world demands such a drug or drug combination which not only prevents the entry of SARS-CoV-2 in the human cell but also ejects it or its material from the body completely. The current computational study not only utilizes a structure-based drug design approach to find possible drug candidates but also explains (i) why the prescription of chiral drugs was not satisfactory, (ii) what types of modification can make their prescription satisfactory, (iii) the mechanism of action of chiral drugs (chloroquine and hydroxychloroquine) to block SARS-CoV-2 from binding to human cells, and (iv) the strength of mefloquine to eliminate SARS-CoV-2. As the main protease (M${}^{pro}$) of microbes is considered as an effective target for drug design and development, the binding affinities of mefloquine with the M${}^{pro}$ of JC virus and SARS-CoV-2 were calculated, and then compared to know the eliminating strength of mefloquine against SARS-CoV-2. The M${}^{pro}$ of JC virus was taken because mefloquine has already shown a tremendous result of eliminating it from the body. The prescription of a combination of S-$(+)$-hydroxychloroquine and $(+)$-mefloquine is considered as a boon by the predicted study.

In this study, the interactions of 7 commercially available BCR-ABL tyrosine kinase enzyme inhibitors with amino acids in the active site of the relevant enzyme were investigated quantum mechanically. Here a per-residue study was carried out. Interaction energies were calculated by using the coordinates of the critical residues in the binding site of the enzyme and the drug molecules docked in this region. DFT methods were used during the QM processes. All interaction energies were calculated via M06-2X functional and 6-31G (d,p) basis set in vacuum. Based on the results obtained, it was tried to be determined which of the important residues in the binding cavity of the enzyme could better interact with the examined ligands. It is thought that this study may contribute to the development of tyrosine kinase enzyme inhibitors.