From the bound ligand and the binding site ?radius was set

From the bound ligand and the binding site ?radius was set to 10A. Docking: Docking studies were performed by using iGEMDOCK as well as by using the automated functions available at the docking server (http://www.dockingserver.com/). The results of docking runs are given in Tables 1 and 2. In order to get accurate docking, stable (slow) docking was used as a default setting. Blind docking runs and repeats of runs with the same compounds were carried out to avoid false positive or false negative results. In iGEMDOCK, the parameters of docking run were set as population size (N = 300), generations (80), number of solutions (10). The best pose was selected based on 12926553 the best conformation that allows the lowest free energy of binding. The docking server [35] is based on MMFF94 force field for energy minimization of ligand molecules. Gasteiger partial charges were added to the ligand atoms. Non-polar hydrogen atoms were merged, and rotatable bonds were defined. Essential hydrogen atoms, Kollman united atom type charges, and solvationOther methodsGeneration of protein surfaces, compounds electrostatic interactions were generated by Molegro Virtual Docker. Hydrogen bonding figures and binding site residues are generated by DS visualizer 3.1.Results and Discussion The rationale behind this studyDuring RNAi, siRNA binds and releases from its binding pocket of the PAZ 3-Amino-1-propanesulfonic acid web domain of Ago proteins in a manner that allows proper coupling with the target mRNA and RNase activity. Unfortunately, little is known about the nature of such interactions. Although, stable or strong binding is expected to interfere with the release of siRNA from the PAZ domain, data investigated this process is lacking. Therefore, in this research, we tried to uncover the forces governing nucleotides recognition by the PAZ domain. We also correlated nucleotide-receptor specific aspects such as total 374913-63-0 web surface of interaction, electrostatic forces, hydrogen bonding and interaction energy with previously characterized RNAi data.Docking resultsA representative figure of the 23727046 best docked poses of compounds is shown in Fig. 2A. Before docking experiments, in either iGEMDOCK or the docking server the docking site was estimated and docking carried out against a predefined site that include ?residues within 10 A from the center of the binding cavity. This was done to allow for possible interactions of compounds composed of dimers or trimers of nucleotides or nucleotide analogues. Furthermore, predefining the active site is helpful to getsiRNA Recognition by PAZ DomainFigure 1. Structure of modified nucleotides or nucleotides analogues used in the docking studies. The figure is generated by ChemBioDraw ultra 12.0 (CambridgeSoft, USA). doi:10.1371/journal.pone.0057140.gsiRNA Recognition by PAZ DomainTable 1. The docking results by using iGEMDOCK.#Ligand cav3MJ0_OMU-t-5.pdb cav3MJ0_OMU-tt-1.pdb cav3MJ0_OMU-ttt-0.pdb cav3MJ0_OMU-u1-2.pdb cav3MJ0_OMU-u2-5.pdb cav3MJ0_OMU-u3-1.pdb cav3MJ0_OMU-u4-9.pdb cav3MJ0_OMU-u5-3.pdb cav3MJ0_OMU-u6-5.pdb cav3MJ0_OMU-u7-6.pdb cav3MJ0_OMU-u8-4.pdb cav3MJ0_OMU-u9-1.pdb cav3MJ0_OMU-u10-3.pdb cav3MJ0_OMU-u11btbt-7.pdb cav3MJ0_OMU-u12-2.pdb cav3MJ0_OMU-u13-2.pdb cav3MJ0_OMU-u14-8.pdb cav3MJ0_OMU-u15bbbb-8.pdb cav3MJ0_OMU-u16-9.pdb cav3MJ0_OMU-u17bnbn-1.pdb cav3MJ0_OMU-u18byby-9.pdb cav3MJ0_OMU-u19bbn-2.pdb cav3MJ0_OMU-u20bb-8.pdb cav3MJ0_OMU-u21rhrh-5.pdb cav3MJ0_OMU-utd1-8.pdb cav3MJ0_OMU-utd2-8.pdbTotal Energy 2104.318 2132.792 2161.759 281.8359 2122.043 2121.332 2.From the bound ligand and the binding site ?radius was set to 10A. Docking: Docking studies were performed by using iGEMDOCK as well as by using the automated functions available at the docking server (http://www.dockingserver.com/). The results of docking runs are given in Tables 1 and 2. In order to get accurate docking, stable (slow) docking was used as a default setting. Blind docking runs and repeats of runs with the same compounds were carried out to avoid false positive or false negative results. In iGEMDOCK, the parameters of docking run were set as population size (N = 300), generations (80), number of solutions (10). The best pose was selected based on 12926553 the best conformation that allows the lowest free energy of binding. The docking server [35] is based on MMFF94 force field for energy minimization of ligand molecules. Gasteiger partial charges were added to the ligand atoms. Non-polar hydrogen atoms were merged, and rotatable bonds were defined. Essential hydrogen atoms, Kollman united atom type charges, and solvationOther methodsGeneration of protein surfaces, compounds electrostatic interactions were generated by Molegro Virtual Docker. Hydrogen bonding figures and binding site residues are generated by DS visualizer 3.1.Results and Discussion The rationale behind this studyDuring RNAi, siRNA binds and releases from its binding pocket of the PAZ domain of Ago proteins in a manner that allows proper coupling with the target mRNA and RNase activity. Unfortunately, little is known about the nature of such interactions. Although, stable or strong binding is expected to interfere with the release of siRNA from the PAZ domain, data investigated this process is lacking. Therefore, in this research, we tried to uncover the forces governing nucleotides recognition by the PAZ domain. We also correlated nucleotide-receptor specific aspects such as total surface of interaction, electrostatic forces, hydrogen bonding and interaction energy with previously characterized RNAi data.Docking resultsA representative figure of the 23727046 best docked poses of compounds is shown in Fig. 2A. Before docking experiments, in either iGEMDOCK or the docking server the docking site was estimated and docking carried out against a predefined site that include ?residues within 10 A from the center of the binding cavity. This was done to allow for possible interactions of compounds composed of dimers or trimers of nucleotides or nucleotide analogues. Furthermore, predefining the active site is helpful to getsiRNA Recognition by PAZ DomainFigure 1. Structure of modified nucleotides or nucleotides analogues used in the docking studies. The figure is generated by ChemBioDraw ultra 12.0 (CambridgeSoft, USA). doi:10.1371/journal.pone.0057140.gsiRNA Recognition by PAZ DomainTable 1. The docking results by using iGEMDOCK.#Ligand cav3MJ0_OMU-t-5.pdb cav3MJ0_OMU-tt-1.pdb cav3MJ0_OMU-ttt-0.pdb cav3MJ0_OMU-u1-2.pdb cav3MJ0_OMU-u2-5.pdb cav3MJ0_OMU-u3-1.pdb cav3MJ0_OMU-u4-9.pdb cav3MJ0_OMU-u5-3.pdb cav3MJ0_OMU-u6-5.pdb cav3MJ0_OMU-u7-6.pdb cav3MJ0_OMU-u8-4.pdb cav3MJ0_OMU-u9-1.pdb cav3MJ0_OMU-u10-3.pdb cav3MJ0_OMU-u11btbt-7.pdb cav3MJ0_OMU-u12-2.pdb cav3MJ0_OMU-u13-2.pdb cav3MJ0_OMU-u14-8.pdb cav3MJ0_OMU-u15bbbb-8.pdb cav3MJ0_OMU-u16-9.pdb cav3MJ0_OMU-u17bnbn-1.pdb cav3MJ0_OMU-u18byby-9.pdb cav3MJ0_OMU-u19bbn-2.pdb cav3MJ0_OMU-u20bb-8.pdb cav3MJ0_OMU-u21rhrh-5.pdb cav3MJ0_OMU-utd1-8.pdb cav3MJ0_OMU-utd2-8.pdbTotal Energy 2104.318 2132.792 2161.759 281.8359 2122.043 2121.332 2.

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