As a new PyRosetta user, I've hit a roadblock regarding score function weights. How do you intelligently choose the weights for your score function? I've seen some scripts (e.g. dG_calc.py) where users arbitrarily set their weights, but how did they determine these weights? Some people have told me that the 'standard' weights should work for most apps, but when I ran the simple poly-alanine fold program (shown in the PyRosetta User Manual) 145 times using the standard weights instead of the custom weights, my poly-alanine chain never folded into an alpha helix. However, the custom weights (VDW 1, hbond_sr_bb 1) listed in the user manual could always lead to a good alpha-helix fold within 2-7 runs. I've heard of the OptE protocol also but I don't know what this is or how to use it and I haven't found any good papers describing it.
So bottom-line is: how do I choose the weights for my score function? My proteins of interest range from 35-100 amino acids and I'm just trying to calculate the stabilities of these proteins.
(Just a note, I'm not familiar with C++ so any advice in terms of python or simple layman language would be helpful!)