----- Original Message ----- From: Thomas Evangelidis <[email protected]> Date: Thursday, June 17, 2010 10:48 Subject: [gmx-users] Energy minimization: problems with ramachanrad score To: [email protected]
> I 'm trying to relax my homology models from steric clashes, and while > searching for the appropriate minimization scheme, I came across this old > thread: > > http://lists.gromacs.org/pipermail/gmx-users/2007-April/027043.html > > The authors in the cited paper have created near-native structures as a test > set with RMSD 1.06 ± 0.14 Å over the native ones. Then they ran energy > minimization in vacuo with l-bfgs for 10000 steps or until convergence to > machine precision and they found that ordinary MM potentials (AMBER99, > OPLS-AA, GROMOS96, and ENCAD) showed no significant improvement on the > structures. On the contrary the last 3 were found to move the conformation > away from the native state by 11%, 40%, and 44% respectively. They also > tested their own 3 hybrid Knowledge-Based / Molecular Mechanics (KB/MM) > potentials and found that the best performing was moving the structures by > 11% closer to the native fold. > > Essentially they claimed that energy minimization with the ordinary MM > potentials is rubbish! I have one remark to make on this. Their decoy set > comprised no-native protein conformers with RMSD ~1A. I'm wondering if the > results will be similar for RMSDs ~3A as in my case where I'm building > homology models with average sequence identity to templates 25-30%? > > And with respect to the original question, if you overdo it with energy > minimization the Ramachandran scores do deteriorate. However if you stop at > an intermediate step you can get the same score, bond lengths and angles but > with less steric clashes. Is this improvement plasmatic as the authors claim, > namely you have moved away from the native fold although stereochemically the > model look good? Without having actually read their paper... there's could easily be a kind of apples-and-oranges comparison going on. The local optimum resulting from a single EM using MM forcefields optimized for non-vacuum conditions on near-native folds in vacuo are being compared with (say) crystal structures for the fitness of those minima as a model of (presumably) what's around under biological conditions. I'd guess that there's an appreciable number of cases where this is a three-way absurdity... Mark
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