On Jun 14, 2010, at 1:22 PM, Francesco Pietra wrote:

Eric: Thanks. Headache adding hydrogen atoms (just as you mentioned addH) with my present system. Neither CHIMERA nor REDUCE were able to treat ASH/ASP HIP/HIE etc as I know from experiments, and software for pKa simulation also dropped. But it may be my fault.

As per the AddH documentation you should be able to get the protonation states you want if you specifically know those states beforehand: Protonation States AddH aims to generate protonation states reasonable at physiological pH. For example, hydrogens are not added to the phosphodiester moieties of DNA and RNA. By default, aspartic acid and glutamic acid sidechains are assumed to be negatively charged, while arginine and lysine sidechains are assumed to be positively charged (although other states can be attained). Two chemical moieties are treated as ambiguous at biological pH: imidazoles such as histidine sidechains; histidine protonation states can be specified by the user or guessed by the method terminal phosphates (the third ionization); if one P–O bond is at least 0.05 Å longer than the others around that same phosphorus atom, that oxygen will be protonated Potentially ambiguous or rare (shifted-pKa) protonation states, especially in binding sites and nonstandard residues, should be verified and corrected as needed. For example, extra hydrogens can be deleted, and atom types can be edited (before hydrogen addition) with setattr or Build Structure. That last part could probably use an example. Let's say you know that the asparagine which is residue 39 in chain A should have atom OD1 protonated. Changing the atom type to O3 (from O2-) [before AddH] would accomplish that: setattr a idatmType O3 :39.a@od1 If you don't know specifically which oxygen should be protonated, this may not be a big help. --Eric Eric Pettersen UCSF Computer Graphics Lab http://www.cgl.ucsf.edu

As to the dockprep with either multiple pdb file, or single files followed by "cat", it seems to me now that the latter is advantageous, One can combine single-molecule mol2 files at will, and modify one or more mol2 files without repeating the whole calculation.

francesco

On Mon, Jun 14, 2010 at 8:29 PM, Eric Pettersen <pett@cgl.ucsf.edu> wrote:

...

On Jun 14, 2010, at 10:48 AM, Francesco Pietra wrote:

With the combined pdb file, does dockprep operate on single molecules one after the other, so that it will not encounter obstacles even for many (more complex) ligands?

I think this will be okay. Chimera ignores sibling submodels (e.g. #0.2 is a "sibling" of #0.1) when adding hydrogens so you will be okay if all your ligands come from one file. --Eric

Eric Pettersen

UCSF Computer Graphics Lab

http://www.cgl.ucsf.edu