Hi modellers,
already a while ago I have noticed that modeller tends to produce what I would call spaghetti proteins (containing knots and other fancy structures) when it is supplied with multiple templates that are far from the target (35 % or less) and also quite diverse among each other.
However, Modeller 9 seems to suffer more from this effect than the previous versions: One of our test cases uses 10 templates with between 86% and 31% sequence similarity to the target. I know that this is not the optimal strategy (especially after reading this paper: http://bioinformatics.oxfordjournals.org/cgi/content/abstract/btm262v1 ) but modeller 8.2 still performed quite well and all 10 models had good topology (close to the 86% template) and secondary structure. However, I now re-run our test with modeller 9.1, using the identical alignment (T-Coffee) and the same input file (below) and the result looks much worse. Most among the 10 generated models show a messed up (swaped) topology, many have knots and the different models are generally more diverse.
So to what extend differs the multiple-template treatment of Modeller 9 from previous versions? Do I need to use different parameters for multi-template modeling in the new version? Or is the general default modeling protocol different now?
So here is our (old-style) input file:
INCLUDE SET OUTPUT_CONTROL = 1 1 1 1 1 SET ALNFILE = 'final.pir_aln' SET KNOWNS = '1K2H_A' '1M31_A' '1J55_A' '1KSO_A' '1MQ1_A' '1MWN_A' '1MHO_' '1NSH_A' '1K8U_A' '1DT7_A' SET SEQUENCE = 'target' # code of the target SET ATOM_FILES_DIRECTORY = '../templates/modeller/' SET STARTING_MODEL= 1 # index of the first model SET ENDING_MODEL = 10 # index of the last model CALL ROUTINE = 'model'
I am attaching a typical result of modeller 8 and one of modeller 9 for comparison.
Thanks in advance for any comments! Best regards, Raik