-- modeller-care@salilab.org http://www.salilab.org/modeller/ Modeller mail list: http://salilab.org/mailman/listinfo/modeller_usage ------------------------------ Message: 3 Date: Tue, 01 Nov 2011 11:55:27 -0700 From: Modeller Caretaker modeller-care@salilab.org Subject: Re: [modeller_usage] automodel.max_molpdf recommended values and usage format To: Andrew Voronkov drugdesign@yandex.ru Cc: modeller_usage@salilab.org Message-ID: 4EB0409F.8050901@salilab.org Content-Type: text/plain; charset=ISO-8859-1; format=flowed On 11/01/2011 10:28 AM, Andrew Voronkov wrote: > how on your opinion modeller objective function correlates with > quality of the models. For example I have objective function value > 1730 for one modelk and -750 which as I understand reflects free > energy. Does it mean that I shouldn t consider the first one at > all? The Modeller objective function is simply a measure of how many restraints were violated in building your model. While the score could be thought of roughly as an "energy" (not free energy) this is certainly not a rigorous measure of model quality. Use an assessment function such as normalized DOPE for this purpose. > Let's say I want to make cutoff -100 for the objective function. In > which format it should be done? > > automodel.max_molpdf -100 Build your models, then assess them and pick the best ones. max_molpdf is designed as a filter to throw away the very worst models - it doesn't act on the final PDF, but the score of intermediate (partially optimized) models - the reasoning being to not waste time on trying to optimize a model that is very bad. Thus max_molpdf is not really what you want here. Ben Webb, Modeller Caretaker -- modeller-care@salilab.org http://www.salilab.org/modeller/ Modeller mail list: http://salilab.org/mailman/listinfo/modeller_usage ------------------------------ Message: 4 Date: Tue, 01 Nov 2011 23:21:23 +0400 From: Andrew Voronkov drugdesign@yandex.ru Subject: [modeller_usage] flexible ligand parametrization using nonstd_restraints(aln) To: modeller_usage@salilab.org Message-ID: 217441320175283@web128.yandex.ru Content-Type: text/plain; charset=utf-8 I have a task to remodel the loop conformation which binds ligand in order to optimize the ligand-protein structure. Structure is X-ray, but ligand position is not known, so I take it from docking assuming that docking gives pose close to correct. So the goal is to model flexibility. I have asked this question couple of days a ago, but now it is more specific. I have used loop modeling with lgiand transfer and it works relatively well, but as I understand as far as this is non conventional residue it is treated as rigid and its interactions with protein are also treated as rigid according to what is written in the manual (listed below). So is it possible to define ligand as flexible using nonst restrains, I need to consult with someone who did. Actually it s kind of usage of Modeller as docking software, I don t knwo whether it is possible to parametrize ligand and optimize its position using simulated annealing and loop rmodeling, so kind of imitating induced fit. Has anyone tried this and question to Modeller Caretaker - is it potentially possible? Best regards, Andrew nonstd restraints(aln) 44 CHAPTER 4. COMPARATIVE MODELING CLASS REFERENCE This routine adds restraints to keep non-standard residues (anything treated as a HETATM or BLK residue, such as ligands or metal ions) in a reasonable conformation. You can override this method if you need to change these restraints. By default, four sets of restraints are built: ? For each residue that has no defined topology (generally BLK residues, used to transfer ligands directly from templates, as described in Section 2.2.1), intra-residue distances are all constrained to their template values. This causes each residue to behave as a rigid body. ? Inter-residue distances are constrained to template values if these are 7?A or less. This has the effect of preserving multiple-HETATM structures such as DNA chains. If the distances are 2.3?A or less they are assumed to be bonds and so are restrained more strongly and also excluded from the nonbonded list. ? Residue-protein atom distances are strongly constrained to template values (and excluded from the nonbonded list) if these are 2.3?A or less. This preserves chemical bonds between ligands and the protein. ? Residue-protein C distances are constrained to template values if these are 10?A or less and are not already bonded by the previous restraints. This preserves the ligand position. - so I get protein-ligand interactions very much restrained and all final models are quite close to the initial coordinates. ------------------------------ _______________________________________________ modeller_usage mailing list modeller_usage@salilab.org https://salilab.org/mailman/listinfo/modeller_usage End of modeller_usage Digest, Vol 10, Issue 136 ***********************************************