Currently I am running Rosetta flexible backbone design (ver. 3.3) to create novel proteins. My problem is, when I add PSSM as a favourable sequence profile, sometimes negative/positive weights behave strangely. The below is my XML code.
[Reweight scoretype=res_type_constraint weight=1.0/]
[FlxbbDesign name=flxbb ncycles=3 constraints_sheet=100.0 sfxn_design=SFXN1 sfxn_relax=SFXN1 clear_all_residues=0/]
[FavorSequenceProfile name=seq weight=1.0 pssm="some_protein.pssm" scorefxns=SFXN1/]
Here I imposed 1.0 as a weight value. For some proteins, "1.0" produces highly sequence identical proteins whereas "-1.0" is beneficial for some proteins. Moreover, in some proteins, whatever values I use (1.0/-1.0), it does not matter. Does anybody have this problem?
I also saw that there is an option called "negative_better" in ver. 3.4. Does it deal with this problem? If so, does it exist it in ver. 3.3 as well?