Comparative study of some energetic and steric parameters of the wild type and mutants HIV‐1 protease: a way to explain the viral resistance

Abstract

Because, in vivo, the HIV‐1 PR (HIV‐1 protease) present a high mutation rate we performed a comparative study of the energetic behaviors of the wild type HIV‐1 PR and four type of mutants: Val82/Asn; Val82/Asp; Gln7/Lys, Leu33/Ile, Leu63/Ile; Ala71/Thr, Val82/Ala. We suggest that the energetic fluctuation (electrostatic, van der Waals and torsion energy) of the mutants and the solvent accessible surface (SAS) values can be useful to explain the viral resistance process developed by HIV‐1 PR. The number and localization of enzyme mutations induce important modifications of the van der Waals and torsional energy, while the electrostatic energy has an insignificant fluctuation. We showed that the viral resistance can be explored if the solvent accessible surfaces of the active site for the mutant structures are calculated. In this paper we have obtained the solvent accessible surface for a group of 15 mutants (11 mutants obtained by Protein Data Bank (PDB) file, 4 mutants modeled by CHARMM software) and for the wild type HIV‐1 PR). Our study try to show that the number and localization of the mutations are factors which induce the HIV‐1 PR viral resistance. The larger solvent accessible surface could be recorded for the point mutant Val 82/Phe.

Heterodimeric interaction and interfaces of S100A1 and S100P

“…The heterodimeric structural template of S100A1 and S100P was constructed by graphically superimposing the structure of the apo-S100A1 monomer [35] on to the X-ray structure of one of the monomers within the calcium-bound S100P dimer. Molecular dynamic simulation of the heterodimeric structure was processed using the CHARMM (Chemistry at HARvard Macromolecular Mechanics) protein structure modelling software [36,37]. First, all proton positions were mapped on to the heterodimeric structural template of the S100P/S100A1 heterodimer at pH 7.0.…”

Repurposing anti-inflammatory drugs for fighting planktonic and biofilm growth. New carbazole derivatives based on the NSAID carprofen: synthesis, in silico and in vitro bioevaluation

“…New carbazole derivatives 1a-i and III were synthesized by nitration, halogenation, N-alkylation followed by subsequent halogenation, starting from the NSAID carprofen and its esters I and II ( Scheme 1 ). Esters I and II were obtained by esterification of commercial carprofen with methanol and ethanol in the presence of H 2 SO 4 ( Avram et al., 2002 ; Favia et al., 2012 ; Dumitrascu et al., 2022 ).…”

“…All chemicals were purchased from Sigma Aldrich (St. Louis, MO, USA), Aladdin Reagent (Shanghai, China). The esters I and II were prepared according to the methods described in previous articles ( Avram et al., 2002 ; Bordei Telehoiu et al., 2020 ; Liu et al., 2021 ). 1 H-and 13 C-NMR spectra were recorded on a Varian Gemini 300BB spectrometer (Varian, Palo Alto, CA, USA) operating at 300 MHz for 1 H and 75 MHz for 13 C. CDCl 3 CD 3 COCD 3 or DMSO-d6, were used as solvent and TMS (δ = 0.00 ppm) as an internal standard.…”

“…3D and Simplified Molecular Input Line Entry (SMILES) files of the compounds 1a - 1i ( Favia et al., 2012 ) were obtained by Molecular Operating Environment (MOE) software ( Avram et al., 2002 ).…”

Current Perspectives on Biological Screening of Newly Synthetised Sulfanilamide Schiff Bases as Promising Antibacterial and Antibiofilm Agents

“…The energies of the structures were minimized using Forcefield MMFF94x with a gradient of 0.05. After minimization, Gasteiger partial charges were applied to all compounds [ 44 ].…”