Dear Rosetta developers, I am wondering whether it is possible to cross-check results between Rosetta++ and Rosetta 3 by using the same scoring function for each.
As an example, I tried evaluating the score of the attached PDB file using the two programs and obtained -79.88 from Rosetta++ and 323.668 from Rosetta 3. I also tried breaking down the energies into components to resolve the difference, without much success.
I've attached a more detailed output below.
The reason I am trying to do this is our lab would like to make use of the protocol outlined in
"Structure-based protocol for identifying mutations that enhance protein-protein binding affinities", Sammond et al.
to design improved binders to glycoprotein hormone receptors. So far we have used the version currently running on the Rosetta Design server, which is based on Rosetta++. We were encouraged by the extensive validation studies performed in the paper, and indeed the results we obtained were encouraging, with the protocol already producing mutations matching those known from the literature.
However we would like to use this protocol to examine protein complexes containing post-translational modifications, support for which is only available in Rosetta 3. Thus I am learning more about the Rosetta internals, in an effort to port increase_affinity from Roestta++ to Rosetta 3 (using PyRosetta).
I am starting this effort by trying to reproduce the Rosetta++ scoring function on Rosetta 3, given that the Sammond results were thoroughly validated against the Rosetta++ function.
Thank you and sincerely,
p.s. if anyone knows any efforts to update increase_affinity to newer scoring functions, or to get it running on Rosetta 3.5, please let me know. We are an experimental group (genetics, Hay lab) and would definitely appreciate any assistance in this direction.
COMMAND: rosetta.gcc -paths ~/Software/Rosetta2/rosetta++/paths.txt -s a.pdb -score -intout test.txt -overwrite -remark_output -scorefile a.score
TOTAL SCORE -79.88
Rosetta 3 (using PyRosetta.ScientificLinux-r56324.64Bit)
from rosetta import *
pose = pose_from_pdb("a.pdb")
scorefxn = get_fa_scorefxn()
print "E = %f" % scorefxn(pose)
TOTAL SCORE 323.668
Weight Raw Weighted
fa_atr 0.8 -302.098 -241.678
fa_rep 0.44 419.826 184.724
fa_sol 0.75 193.97 145.477
fa_intra_rep 0.004 202.386 0.81
fa_elec 0.7 -19.301 -13.511
pro_close 1 28.542 28.542
hbond_sr_bb 1.17 -5.507 -6.443
hbond_lr_bb 1.17 -14.493 -16.957
hbond_bb_sc 1.17 -2.204 -2.579
hbond_sc 1.1 -1.476 -1.623
dslf_fa13 1 -5.318 -5.318
rama 0.2 -7.836 -1.567
omega 0.5 35.077 17.538
fa_dun 0.56 430.751 241.22
p_aa_pp 0.32 -16.289 -5.212
ref 1 0.245 0.245