Is truly meant with this If all 4 models had already the maximal possible variety of salt bridges, then they ought to all four be rather related, and MD optimization wouldn’t achieve a lot further. As documented inside the manuscript (Table 1 and Added files), the three structures that have been obtained by distinct docking computer software tools have been very distinct. They offered diverse salt bridges as well as the numbers of salt bridges were distinctive. Additionally, inside the case of the PatchDock’ structure the number of salt bridges improved considerably right after power minimization (Table 1). The Reviewer is really suitable that application with the MD routine did not boost the number of salt bridges any additional. 20) “..manual adjustment yielded..” generally worries me a little and may need to have a little a lot more justification. 21) “.. Thus, for the duration of manual editing, we adjusted the position of this loop in all model structures to provide salt bridge partners..” how was this done Authors’ response: During manual editing and further evaluation of model structures we used the presence of salt bridges such as functionally vital (as shown by experiments) residues because the most important criteria. Hence, through manual editing we’ve got adjusted the amino acid positions, if such an adjustment yielded a new salt bridge and did not require significant disturbance on the structure. In one particular case, we succeeded to slightly tilt the entire molecule of cytochrome c, supplying salt bridge partners for the four functionally most important lysine residues (the PatchDock’ structure). The difference between the model structures, as provided by distinct docking routines, may be, to some extent, precise to the interaction studied. Indeed, the smaller globule of cytochrome c is nearly evenly and densely covered by 18 lysine residues; just about each and every of them can potentially make a salt bridge with acidic residue (s) of a WD domain. In the revised manuscript, we explicitly state that while our model structure might be a Talsaclidine GPCR/G Protein non-unique option since it concerns the orientation of cytochrome c, this model structure enabled the identification of the three acidic duplets of Metolachlor References Apaf-1 that, on one hand, are involved in complex, bifurcated bonds using the lysine residues of cytochrome c and, alternatively, show a distinct evolutionary pattern, appearing only within Chordata, concomitantly with all the look in the cytochrome c-dependent apoptotic pathway.Shalaeva et al. Biology Direct (2015) ten:Page 24 ofSince only three acidic duplets of Apaf-1 are within a position to interact with cytochrome c (see Figs. four and ten), we believe that these acidic pairs might bind cytochrome c, hence triggering the apoptosome formation. 22) “..and in each and every of these models, lysine residues of cytochrome c formed many salt bridges..” how quite a few lysines did this, all of them Quantify, please. Authors’ response: A list of all lysine-involving salt bridges for every single model, calculated just before and following power minimization, is presented in Table 1. 23) “.. Notably, the ClusPro model changed insignificantly soon after energy minimization, even though the manually edited PatchDock’ model gained 6 new salt bridges..” this probably will be the outcome of one docking server using EMMD as well as the other not, or both employing distinct force fields, among which is similar to yours Authors’ response: The ClusPro server applied a MD method using the CHARMM force field, similar as we employed within the MD simulations, so the consistency of power minimization final results was expected. The oth.
