Molecular dynamics simulations on interaction between bacterial proteins: Implication on pathogenic activities

Abstract

We perform molecular dynamics simulation studies on interaction between bacterial proteins: an outer-membrane protein STY3179 and a yfdX protein STY3178 of Salmonella Typhi. STY3179 has been found to be involved in bacterial adhesion and invasion. STY3178 is recently biophysically characterized. It is a soluble protein having antibiotic binding and chaperon activity capabilities. These two proteins co-occur and are from neighboring gene in Salmonella Typhi-occurrence of homologs of both STY3178 and STY3179 are identified in many Gram-negative bacteria. We show using homology modeling, docking followed by molecular dynamics simulation that they can form a stable complex. STY3178 belongs to aqueous phase, while the beta barrel portion of STY3179 remains buried in DPPC bilayer with extra-cellular loops exposed to water. To understand the molecular basis of interaction between STY3178 and STY3179, we compute the conformational thermodynamics which indicate that these two proteins interact through polar and acidic residues belonging to their interfacial region. Conformational thermodynamics results further reveal instability of certain residues in extra-cellular loops of STY3179 upon complexation with STY3178 which is an indication for binding with host cell protein laminin.

Computer-aided synthesis of dapsone-phytochemical conjugates against dapsone-resistant Mycobacterium leprae

“…However, the generated simple scoring functions or docking scores obtained through docking program often disregards the noteworthy energetic contributions as solvation free energy, which is not ideal for the calculation of the binding affinity and correct binding pose of any small molecule or ligands. Hence, the exact ligand-binding pose was considered by integrating the docking program, all-atoms MD simulations and the binding free energy MM/PBSA method, since the latter approach had been seen as a practical and trustworthy approach to model molecular recognition mechanisms involving receptor-ligand binding interactions [17][18][19] . Amongst the popular classical simulation methods, the MM/PBSA method had been considered a valid and reliable way to model molecular recognition, including receptor-ligand binding interactions 1,20,21 .…”

“…All-atom molecular dynamics simulation study. The dynamic behaviours of each MlDHPS DDS/ DPCs complex was investigated using all-atom molecular dynamics simulations using Amber-99sb ILDN force field in TIP3 water models employed in GROMACSv5.1 1,[17][18][19] . A three-step approach was employed for simulation studies, which include heating the system followed by equilibration and at the last the production run at 300 K for 40 ns for each system.…”

“…Gromacs utility tools were employed for trajectory analysis. The quality assurance parameters like backbone RMSD, C-alpha root mean square fluctuations, a radius of gyration and intermolecular hydrogen bonds were computed using gmx rms, gmx rmsf, gmx gyrate, and gmx hbond utility toolkits of GROMACS 17,18 . Two-dimensional graphs depicting the dynamic stability were plotted using the Xmgrace tool.…”

“…BIOVIA DSV was used to compute the inter-molecular interaction. In order to observe the highest amplitude records and correlated motions in complex systems, the most potent statistical technique, principal component analysis (PCA) was employed 1,[17][18][19] . In this study, the covariance matrix of Cα-atoms of the complex systems was built using gmx covar tool.…”

“…The procedure for calculation of binding free energy was adopted from previous studies 1, 17-19 . Synthesis and structural interpretation of Dpcs. An ice-cool sodium nitrite solution of molarity equal to DDS was added dropwise with an 8 mL volume of concentrated HCl, and 8 mL water serially on an ice bath; after completion of the diazotization, the reaction was followed by pouring of ice-cool solution of 0.03 mol of individual phytochemicals in volumes of 20 mL 10% sodium hydroxide solution, as described earlier 1,9,17 . The resultant mixture was maintained at pH 5 to 6, and the obtained products were filtered and recrystallized with ethanol.…”