Hello, I tested local docking of AlphaRED (ReplicaDock2) protocol. As the mc steps, the fa_rep score increases rapidly.
Checking a trajectory with high fa_rep score, there are clashes between some residues. (e.g. 1st score and 2000th score)
SCORE: score fa_atr fa_rep motif_dock atom_pair_constraint omega p_aa_pp rama_prepro I_sc temp_level temperature rms maxsub
SCORE: -1242.286 -3616.527 2487.477 -320.722 0.000 269.748 -98.770 36.507 689.825 1.000 0.800 0.036 627.000
SCORE: 34813.739 -3880.623 38639.354 -208.596 0.000 278.419 -92.060 77.245 -67.071 2.000 1.500 1.113 627.000
I figured out that the backrub steps cause those unfolding or clashes.
Is this a normal production of backrub? To prevent this, how do I change the script?
Or is there any better way to change the conformation of specific residues?
Here is the rosetta script that I used. I used n_struct=4 and n_replica=3. I am using rosetta-356 version
<ROSETTASCRIPTS>
<SCOREFXNS>
<ScoreFunction name="score_dock_low" weights="muds_2021"/>
</SCOREFXNS>
<FILTERS>
</FILTERS>
<RESIDUE_SELECTORS>
<BFactorSelector name="bfactor" lower_bfactor="0.0" upper_bfactor="80.0" lower="1" upper="1" min_contiguous_res="4"/>
<StoredResidueSubset name="get_plddt" subset_name="plddt"/>
</RESIDUE_SELECTORS>
<MOVE_MAP_FACTORIES>
<MoveMapFactory name="flexRes">
<Backbone residue_selector="get_plddt"/>
<Chi residue_selector="get_plddt"/>
</MoveMapFactory>
</MOVE_MAP_FACTORIES>
<SIMPLE_METRICS>
</SIMPLE_METRICS>
<MOVERS>
<!-- setup jumps and constraints-->
<SwitchResidueTypeSetMover name="switch2fullatom" set="fa_standard" />
<DockSetupMover name="setup_jump"/>
<StoreResidueSubset name="store_subset" residue_selector="bfactor" subset_name="plddt"/>
<RigidBodyPerturbNoCenter name="rb_mover" rot_mag="0.5" trans_mag="1"/>
<HamiltonianExchange name="h_exchange" temp_file="hamiltonians_cen.txt" temp_stride="1000" stats_file="tempering.stats"/>
<DockingInitialPerturbation name="init_pert" slide="1"/>
<TrialCounterObserver name="count" file="trial.stats"/>
<SilentTrajectoryRecorder name="traj" score_stride="1" stride="1" cumulate_replicas="1" />
<Backrub name="bbmover" movemap_factory="flexRes" require_mm_bend="0"/>
<MetropolisHastings name="sampler" trials="1000" scorefxn="score_dock_low">
<Add mover_name="h_exchange"/>
<Add mover_name="traj"/>
<Add mover_name="count"/>
<Add mover_name="rb_mover"/>
<Add mover_name="bbmover" sampling_weight="1"/>
</MetropolisHastings>
</MOVERS>
<PROTOCOLS>
<Add mover_name="store_subset"/>
<Add mover_name="setup_jump"/>
<Add mover_name="init_pert"/>
<Add mover_name="sampler"/>
</PROTOCOLS>
</ROSETTASCRIPTS>
hamilitonians_cen.txt is the same as the provided file.
GRID_DIM 1
GLOBAL_PATCH atom_pair_constraint = 5
1 0.8 muds_2021 NOPATCH fa_rep *= 1.0
2 1.5 muds_2021 NOPATCH fa_rep *= 0.75
3 3.0 muds_2021 NOPATCH fa_rep *= 0.5
#ETABLE FA_STANDARD_SOFT10 fa_rep *= 1.1
Thanks for your assistance.
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