Journal of biomolecular structure & dynamics
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J. Biomol. Struct. Dyn. · Jan 2021
Applying high throughput and comprehensive immunoinformatics approaches to design a trivalent subunit vaccine for induction of immune response against emerging human coronaviruses SARS-CoV, MERS-CoV and SARS-CoV-2.
Coronaviruses (CoVs) cause diseases such as severe acute respiratory syndrome (SARS), Middle East respiratory syndrome (MERS), and coronavirus disease 2019 (COVID-19). Therefore, this study was conducted to combat major CoVs via a trivalent subunit vaccine, which was engineered by implementing sequences of spike (S) protein, nucleocapsid (N), envelope (E), membrane (M) protein, non-structural protein (nsp) 3, and nsp8 antigens. The CTL, HTL, MHC I, and IFN-γ epitopes were predicted via CTLPRED, IEDB, and IFN epitope servers, respectively. ⋯ In summary, investigations demonstrated that this next-generation approach might provide a new horizon for the development of a highly immunogenic vaccine against SARS-CoV, MERS-CoV, and SARS-CoV-2. Communicated by Ramaswamy H. Sarma.
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J. Biomol. Struct. Dyn. · Sep 2020
In silico investigation of spice molecules as potent inhibitor of SARS-CoV-2.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel infectious disease that is in rapid growth. Several trials are going on worldwide to find a solution for this pandemic. The viral replication can be blocked by inhibiting the receptor-binding domain (RBD) of SARS-CoV-2 spike protein (SARS-CoV-2 RBD Spro) and the SARS-CoV-2 main protease (SARS-CoV-2 Mpro). ⋯ We anticipate immediate wet-lab experiments and clinical trials in support of this computational study that might help to inhibit the SARS-CoV-2 virus. Communicated by Ramaswamy H. Sarma.
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J. Biomol. Struct. Dyn. · Jun 2019
Investigation of intermolecular interactions and stability of verubecestat in the active site of BACE1: Development of first model from QM/MM-based charge density and MD analysis.
Alzheimer disease (AD) is a cruel neurodegenerative disorder caused by the deposition of amyloid β (Aβ) peptide inside the brain. The β-secretase (beta amyloid precursor protein (APP) cleaving enzyme 1, BACE1) is one of the enzymes involved in the cleavage of APP that leads to the Aβ formation and it is the primary target for the treatment of AD. Recent report outlines that verubecestat molecule strongly inhibits BACE1; however, its structure, binding mechanism and the stability in the active site of BACE1 are not yet known. ⋯ The MM-generalized Born surface area and MM-Poisson Boltzmann surface area free energy calculations of verubecestat-BACE1 also confirm the high binding affinity of verubecestat. Communicated by Ramaswamy H. Sarma.
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J. Biomol. Struct. Dyn. · Sep 2018
Investigation on the binding mechanism of loratinib with the c-ros oncogene 1 (ROS1) receptor tyrosine kinase via molecular dynamics simulation and binding free energy calculations.
The c-ros oncogene 1 (ROS1) has proven to be an important cancer target for the treatment of various human cancers. The anaplastic lymphoma kinase inhibitor crizotinib has been granted approval for the treatment of patients with ROS1 positive metastatic non-small-cell lung cancer by the Food and Drug Administration on 2016. However, serious resistance due to the secondary mutation of glycine 2032 to arginine (G2032R) was developed in clinical studies. ⋯ Calculations of binding free energies indicate that G2032R mutation significantly reduces the binding affinity of loratinib for ROS1, which arose mostly from the increase of conformation entropy and the decrease of solvation energy. Furthermore, detailed per-residue binding free energies highlighted the increased and decreased contributions of some residues in the G2032R mutated systems. The present study revealed the detailed inhibitory mechanism of loratinib as potent WT and G2032R mutated ROS1 inhibitor, which was expected to provide a basis for rational drug design.
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J. Biomol. Struct. Dyn. · Jan 2014
Interaction between hydroxyethyl starch and propofol: computational and laboratorial study.
Hydroxyethyl starch (HES) is one of the most used colloids for intravascular volume replacement during anesthesia. ⋯ Propofol and HES form a complex with different physical-bio-chemical behavior than the single drugs, which may be an important drug interaction. Further studies should evaluate its clinical effects.