Computational protocol: Sulfonanilide Derivatives in Identifying Novel Aromatase Inhibitors by Applying Docking, Virtual Screening, and MD Simulations Studies

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Protocol publication

[…] Sulfonanilide derivatives are known to suppress aromatase activity in transfected MCF-7 cells []; however their binding potency has not been tested. Therefore several sulfonanilide derivatives were used for the present investigation. 81 sulfonanilide derivatives were drawn on the Marvin sketch tool (, Supplementary 1, in Supplementary Material available online at Further, energy minimization with CHARMm force field was applied. The selected 81 compounds were designed based on nimesulide as described by Su et al., Figures and [], and were imported onto the DS v4.5. Additionally, the known inhibitors, namely, anastrozole, exemestane, letrozole, and tamoxifen, were also sketched on Marvin sketch and were subsequently imported onto the DS v4.5. [...] To further affirm the potentiality of the selected compounds and to evaluate the dynamic behaviour of the prospective drug molecules in the binding site pocket, they were subjected to MD simulation along with the reference compound using GROMACS 4.5.7 [–], employing CHARMm27 [] force field. Ligand topologies were generated using SwissParam []. Corresponding counterions were added to neutralize the solvated TIP3P water model present in the dodecahedron box. Unwanted contacts from the initial structure were dislodged by performing the energy minimization, adapting the steepest descent algorithm which was followed by the NVT and NPT equilibration steps. During this process, the solvent molecules along with the counterions were allowed to move restraining the protein backbone. Both the processes were executed by 100 ps at 300 K and a pressure of 1 bar, respectively. Parrinello-Rahman barostat was employed to maintain the pressure of the system []. The geometry of the water molecules and the bonds involving hydrogen atoms were constrained employing SETTLE and LINCS, respectively [, ]. Particle Mesh Ewald (PME) method [] was used to calculate long-range electrostatic interactions. A cut-off distance of 12 Å was attributed for Coulombic and van der Waals interactions. The equilibrated structures were then subjected to production MD conducted for 50 ns and the results were evaluated on VMD [] and DS. […]

Pipeline specifications

Software tools Marvin, CHARMM, GROMACS, SwissParam, P-LINCS, VMD
Applications Drug design, Protein structure analysis
Organisms Homo sapiens
Diseases Breast Neoplasms, Neural Tube Defects