To add to the discussion, could I raise a relevant question about generating ESP (Apologies to Jiri if this distracts too much from your initial thread).
In our structure in hand, the density for two conformations of the side chain are clearly seen and they could be modeled. This brings a bit of problem because the positive charge becomes more prominent with two conformations there than with one. So what do we usually do when generating ESP for such structures with alternate conformations? Do we remove one before the calculation? PS - I use online PDB2PQR server to do my calculation with PARSE field. I did notice from some old archived discussion on the Web that it ignores one conformation by default. But this seemingly is not the case in newer versions? Regards Sam School of Life Sciences, CUHK On 2 December 2017 at 02:59, Robbie Joosten <robbie_joos...@hotmail.com> wrote: > If you cannot trust the surface of your protein, perhaps you should not > look at the the potential on the surface. Instead you can look at the field > around your protein. This is less precise, but also less sensitive to local > errors. If you want to know how your peptide finds your protein, this is > actually more informative anyway. > > There must be several programs that do this. I have done this for MHC in > the past with YASARA. It really explained nicely how he peptide moved in. > > > > Cheers, > > Robbie > > > > Sent from my Windows 10 phone > > > ------------------------------ > *From:* CCP4 bulletin board <CCP4BB@JISCMAIL.AC.UK> on behalf of Dale > Tronrud <de...@daletronrud.com> > *Sent:* Friday, December 1, 2017 7:29:01 PM > *To:* CCP4BB@JISCMAIL.AC.UK > *Subject:* Re: [ccp4bb] Electrostatic Potential: Poisson-Boltzmann > > These are not easy questions to answer. Certainly atoms, > particularly ones that are charged, even with fractional charges, have a > strong effect on the ESP. If you delete them because you don't know > exactly where they are you will get a different answer than if you put > them in in some reasonable but unsupported location (as you have found). > This result indicates that the peptide does affect the ESP > significantly and you have to consider it. > > You could build lots of models with the peptide in different > conformations and average all the maps. This misses the point. You > have uncertainty in your model which means that you have uncertainty in > your electrostatic potential. Any particular ESP that you calculate and > draw conclusions from will have a large uncertainty and you must > consider that uncertainty when deciding between your potential > conclusions. (I'm not sure if the pun is intended or not!) > > I suppose you could believe that each possible conformation exists to > some extent in reality which means that all the ESP's you calculate > exist in some fraction of the molecules in the cell. It is possible > that only the molecules with a particular conformation of this peptide > have the ESP that allows the molecule to function. Life is hard. > > Another issue that you must consider: If the exact conformation of > this loop causes changes to the ESP that you consider significant to > your understanding of the function of this protein, the presence and > conformation of neighboring proteins and solvent will also cause > significant changes to the ESP. The biological context of the protein > becomes important. If your interpretation depends critically on the > value and distribution of ESP then I'm not sure you can work this out > based on calculated ESP, considering the large uncertainty. > > Dale Tronrud > > > On 12/1/2017 10:02 AM, chemocev marker wrote: > > Hi > > > > I am calculating the Electrostatic Potential of my protein. But there > > were few flexible region with high B-factor and I deleted that part of > > the protein and then recalculated it. But there I can see a big > > change.As I have a structure in the presence and the absence of the > > peptide and the these flexible regions have a better map in the > > structure without peptide and with peptide I have to delete them. > > I have a question, should I model these missing regions > > > > or > > > > I should ignor them > > > > best > > > > Jiri >
