Targeting shikimate pathway: In silico analysis of phosphoenolpyruvate derivatives as inhibitors of EPSP synthase and DAHP synthase

Analysis of Kojic Acid Derivatives as Competitive Inhibitors of Tyrosinase: A Molecular Modeling Approach

“…Different studies have reported that KA derivatives act as inhibitors of tyrosinase [ 19 , 21 , 22 , 23 ]. Initially, we investigated the selectivity of fourteen KA derivatives against the tyrosinase binding pocket using molecular docking, a computational tool widely applied in structure-based virtual screening approaches [ 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 ]. First, re-docking simulations using the crystallographic structure of KA were performed in the CSD Gold [ 33 ] program to validate our docking protocol.…”

“…Despite the relevance of metals for catalysis and structural stability of enzymes, the MD simulations of metal–enzyme systems are a challenge in molecular modeling [ 55 , 66 , 67 ]. The dummy atoms model [ 37 ] represents an advance in the description of these enzymatic systems, since this model captures the structural and electrostatic effects through the introduction of fictitious atoms around the metal ion, redistributing the charges and reducing the excessive repulsion in the metal region.…”

“…The pairwise energy decomposition indicates the energetic contributions (electrostatic and Van der Waals) of each residue involved in the stabilization of the ligands with the enzyme binding pocket. This computational method has been applied to describe protein–protein [ 50 , 70 , 76 , 77 ] and ligand–protein interactions [ 55 , 78 , 79 , 80 , 81 ].…”

In silico identification of novel allosteric inhibitors of Dengue virus NS2B/NS3 serine protease

“…Consensual docking is an approach that consists of combining the results obtained by different scoring functions and ranking them, according to the combination of the results, improving the results obtained and compensating for the deficiencies found in each scoring function.14 Thus, consensus analysis is considered more efficient than single scoring for molecular docking and represents an effective way to achieve better hit rates in various VS studies. 15,16 In both programs, the fluctuation of the enzyme and the ligands was not allowed. Therefore, we analyzed the docking results using different protocols to obtain the most consistent binding affinity of the ligands.…”

Investigation of the target-site resistance of EPSP synthase mutants P106T and T102I/P106S against glyphosate

“…29 Thus, computational methods have been applied to investigate the structural impact of mutations on different enzymes to analyze the stability and affinity of ligand binding, as well as possible conformational changes at the catalytic pocket that lead to impairment of enzymatic activity. [30][31][32][33][34] Recently, we used the free energy surface and quantum mechanics/molecular mechanics (QM/MM) approach to study the catalytic mechanism of EPSPS and the individual roles of catalytic residues Asp313 and Glu341. 5 In the present study, we applied different computational methods, molecular dynamics (MD) simulations and binding free energy calculations, to explore the molecular interactions involved with the site-directed mutations in the EPSPS structure of C. sumatrensis (mutant, P106T) and E. indica (mutant, T102I/P106S).…”