Hey all! I am trying to minimize a few enzymes that are approx 500 residues long. Currently, we are basing our minimization technique on Kellogg et al. which includes repacking the enzymes and then minimizing the entire enzyme with constraints on the backbone. Does anyone know if this seems like a good approach? Even with just the regular minimization with no repacking, we were able to get scores in the -1,000 to -1,200 range but I don't know what else I should be doing to make sure that I am getting the best minimization possible. Any ideas would be greatly appreciated!
Are these from crystal structures? If so, minimising against a ccp4 map is an alternative way to constrain it —PDBe has ED maps, while RCSB has only reciprocal space maps (mtz) on offer. You might not get the lowest folding ∆G even if you keep key crystalline waters and fix the protonation of the active site, but it would be faithful to the crystal structure solution.