Souring control in fluid samples of oil industry using a multiple ligand simultaneous docking (MLSD) strategy

Abstract

We have used docking techniques in order to propose potential inhibitors to the enzymes adenosine phosphosulfate reductase and adenosine triphosphate sulfurylase that are responsible, among other deleterious effects, for causing souring of oil and gas reservoirs. Three candidates selected through molecular docking revealed new and improved polar and hydrophobic interactions with the above-mentioned enzymes. Microbiological laboratory assays performed subsequently corroborated the results of computer modelling that the three compounds can efficiently control the biogenic sulfide production.

Analysis of interactions between potent inhibitors of ATP sulfurylase via molecular dynamics

“…[1] Tests in vitro showed bioactivity of inhibitor combinations against SRB confirming that the reduction of inhibitors' dose and resistance minimisation of bacteria is the outcome of synergism. [1] The combination was evaluated through simultaneously docking of three ligands ABTS, BHA and BHT in the binding site of protein ATPs. This is, because multiple ligands affect the binding mode and free energy due to synergism with each other or by simple additive effects.…”

“…[1] The three ligands were docked in a box defined around the binding site of the protein (PDB code 1V47) whose centre is under the coordinates of APS (214.006, 56.184, 182.237) [1] using Autodok Vina. [15] The protocol used for multiple docking consists of docking the ligand in enzyme and after that the complex was minimised in such a way that the resulting structure served as the target for the next ligand, and so on.…”

“…[15] The protocol used for multiple docking consists of docking the ligand in enzyme and after that the complex was minimised in such a way that the resulting structure served as the target for the next ligand, and so on. [1] The MD simulations were performed using the GROMACS 3.3.2 package. [16] We used a CPU Athlon II X2 B28 with 4 GB of memory RAM, ffg53a6 force field.…”

“…For the quantification of synergism we calculated the sum of the absolute binding free energies for the individual inhibitors which is 31.40 kJ/mol against 2 11.15 kJ/mol for relative binding free energies so there is great synergetic energy between inhibitors, differently of docking [1] in which the simulations showed sub-activity. The difference between the results in the experiments is mainly due to conformational changes in inhibitors and protein which were taken into account.…”

“…The experimental results showed that inhibition was more effective when using the combination of inhibitors. [1] However, experimental data and molecular docking are insufficient to determine the reaction mechanisms of complex protein/inhibitor and inhibitor/inhibitor, particularly those associated with the amount of hydrogen bonds that seems to be joined with the synergic effect. [1] Therefore, the use of molecular dynamics can help us to reveal the molecular mechanisms that lead to such synergistic interactions, especially the amount of hydrogen bonds formed between ligands and also the conformational changes of the ligands and enzyme.…”