Mon Jun  9 09:09:01 PDT 2008
T0440
Make started Mon Jun  9 09:09:52 PDT 2008
Running on peep.cse.ucsc.edu

Mon Jun  9 09:14:20 PDT 2008 Kevin Karplus

T0440 has a good pdb-blast hit to 2yxoA, which is Histidinol Phosphate
Phosphatase.  It has iron, zinc, and sulfate bound, so I should look
for metal-binding sites and add constraints as scaffolding to preserve
them.

Mon Jun  9 09:56:12 PDT 2008 Kevin Karplus

The t06 multiple alignment contains three PDB files:
	2yxoA
	1m65A
	2anuA

Mon Jun  9 13:43:41 PDT 2008 Kevin Karplus

Those three PDB templates naturally come up as the top hits.
Related, somewhat more distant hits are 2hnhA and 1v77A.
try1 will be based mainly on 2yxoA.

Mon Jun  9 17:38:45 PDT 2008 Kevin Karplus

try1-opt3 looks pretty good, but needs some gap closing.

Tue Jun 10 05:37:08 PDT 2008 Kevin Karplus

For try2, I'll turn off maybe_metal and maybe_ssbond, though I wonder
whether C185 and C233 interact.

Highly conserved residues are mainly HIS, charged residues, and C12.
They are the ones for which scaffolding will be needed, but I won't
bother with that yet.  Maybe when I get around to try3.


Tue Jun 10 13:54:01 PDT 2008 Kevin Karplus

The crucial residues seem to be H6,H8, H40, H181, D222, C12.

Here are some distances measured from the alignment to 2yxoA
Distance CYS12.SG-HIS14.ND1: 3.346
Distance HIS14.NE2-HIS260.NE2: 3.449
Distance HIS260.NE2-HIS8.NE2: 3.965
Distance HIS40.NE2-HIS8.ND1: 3.525
Distance HIS40.NE2-HIS14.NE2: 3.310
Distance ASP258.OD1-HIS6.NE2: 2.994
Distance ASP258.OD1-HIS40.NE2: 5.701
Distance HIS181.NE2-HIS6.NE2: 5.811
Distance ASP258.OD2-ASP222.OD2: 5.304


For try3, I'll run again from alignments, but with the try2 sheets and
helices and the distances above as constraints.

Fri Jun 13 18:43:51 PDT 2008 Kevin Karplus

Both MQAU and MQAC like the Zhang-Server models.
Looking at Zhang-Server_TS1, I like it too.

The try3 run has some bad breaks, and both try1-opt3 and try2-opt3
score better with the try3 costfcn.

I should do a break-closing run from the try1 through try3, before
bringing in the metaservers.

Fri Jun 13 18:49:22 PDT 2008 Kevin Karplus

metaserver runs and try4 run started.

I might later want to do a metaserver run with sheet and helix
constraints from a good model, instead of just the try1 metaserver.

costfcn		top models
try1		try4-opt3	MQAC1-opt3.gromacs0	MQAU1-opt3.gromacs0	try2-opt3.gromacs0	try1-opt3.gromacs0
try2		try4-opt3	try2-opt3		MQAC1-opt3.gromacs0	MQAU1-opt3.gromacs0	try1-opt3.gromacs0.repack-nonPC
try3		try4-opt3	try2-opt3		MQAC1-opt3.gromacs0	MQAU1-opt3.gromacs0	try1-opt3.gromacs0.repack-nonPC
try4		try4-opt3	try2-opt3.gromacs0	MQAC1-opt3.gromacs0.repack-nonPC	MQAU1-opt3.gromacs0	try1-opt3.gromacs0.repack-nonPC

rosetta	try2-opt3.gromacs0.repack-nonPC	try4-opt3.gromacs0.repack-nonPC	try1-opt3.gromacs0.repack-nonPC	MQAC1-opt3.gromacs0.repack-nonPC	MQAU1-opt3.gromacs0.repack-nonPC

The biggest disagreements among the top models are for R132-A155
M48-M63 F191-E202.

MQAU1-opt3 and MQAC1-opt2 are both based on Zhang-Server_TS4
I'm afraid I like their loops better than our own from try4-opt3.
Hmm, maybe not for R132-F152, as the MQAC1 and try4 models disagree
about the phase of the helix Q156-K174 in try4 or F152-D170 in MQAC1.

I'll have to think about the phase of the helix---the MQAC1 version
may well be better.

Sat Jun 14 14:37:49 PDT 2008 Kevin Karplus

The try5 costfcn dakes helix and sheet constraints from MQAC1-opt3,
but still likes try4 and try2 better than the MQAC-opt3 models.
I think I'll try polishing the MQA models with try5, to see if I can
get models with comparable breaks and clashes to compare.

Thu Jun 19 12:00:19 PDT 2008   SAM-T08-MQAO hand QA T0440 Submitted
Thu Jun 19 12:00:19 PDT 2008   SAM-T08-MQAU hand QA T0440 Submitted
Thu Jun 19 12:00:19 PDT 2008   SAM-T08-MQAC hand QA T0440 Submitted


Tue Jun 24 20:58:20 PDT 2008 Kevin Karplus

I rather like try5-opt3.  I should make dimers based on try4 and try5
using 2yxoA, and see which optimizes better.

Tue Jun 24 21:22:17 PDT 2008 Kevin Karplus

dimer/try6 started to optimize the try4 dimer
dimer/try7 started to optimize the try5 dimer.

The dimerization interface from 2yxo A/B is rather small, so I don't
think that optimizing in the dimer context is really going to make
much difference.  I wonder if I should check whether PQS has a
different dimer interface.

Wed Jun 25 04:10:32 PDT 2008 Kevin Karplus

dimer/try6 did not improve much on try4, but dimer/try7 did improve on try5.
I don't think that the dimer context really helped any, as the
interface was small, and the optimization in dimer/try7 just moved the
monomers apart a bit to avoid clashes

I should do one more monomeric optimization of each of the dimer
chains, and submit what I have.

Wed Jun 25 04:27:34 PDT 2008 Kevin Karplus

try8 started (excluding try5 and try7 models) to optimize try6
try9 started to optimize try7

Wed Jun 25 11:08:53 PDT 2008 Kevin Karplus

try9 crashed with 
undertaker: Spot.cc:172: XYZpoint Spot::get_spot(const ChainsResiduesAndAtoms*, int, const Pointlist&, const Conformation*, bool, const Spot*) const: Assertion `return_point.mag2() < 1.e12' failed.

I'll try running it again and hope it doesn't tickle the same bug.

Sat Jun 28 07:21:10 PDT 2008 Kevin Karplus

try9 finished fine the second time, and try9-opt3 scores best with the
try9 and try8 costfcns, though rosetta likes best
try8-opt3.gromacs0.repack-nonPC

There is really very little difference between try9 and the MQAC1
model it started from, several runs ago.  The difference between the
MQAC1 series and the try1 series ending with try8-opt3 is a little
bigger, but still pretty small.

I'm scoring all the models (including the server models) with
try10.costfcn, which is the same as try9.costfcn, except for adding a
missing_atoms term to eliminate the incomplete models.

Sat Jun 28 07:39:15 PDT 2008 Kevin Karplus

The top server model with the try10 costfcn is YASARA_TS1.
I'll do another metaserver run using ALL the server models
and the try10 costfcn.

After that, I'll submit 

ReadConformPDB T0440.try9-opt3.pdb	# < dimer/try7-opt3 < try5-opt3 < MQAC1-opt3.gromacs0
ReadConformPDB T0440.try8-opt3.gromacs0.repack-nonPC.pdb	# < dimer/try6-opt3 < try4-opt3< try2-opt3 < try1-opt3 < align(2yxoA)
ReadConformPDB T0440.try5-opt3.pdb	# < MQAC1-opt3.gromacs0
ReadConformPDB T0440.try4-opt3.pdb	# < try2-opt3 < try1-opt3 < align(2yxoA)
ReadConformPDB T0440.MQAU1-opt3.gromacs0.pdb	# < Zhang-Server_TS4 

except for replacing one of try4/try5 with the new metaserver model.
If the new model comes out really good, I might do another run trying
to polish it.


Sat Jun 28 07:49:22 PDT 2008 Kevin Karplus

I just looked at YASARA_TS1, and I don't like its loops all that much.
Q186-S200 may be better than in try9 though, so I might want to copy
that---it depends on which helix needs extending more.  T225-T236 is
also interesting.

Sat Jun 28 08:51:12 PDT 2008 Kevin Karplus

The try10 metaserver run favors MULTICOM-REFINE_TS5

Sat Jun 28 13:34:11 PDT 2008 Kevin Karplus
try10.costfcn still likes try9-opt3 best, but try10-opt3.gromcas 0
comes in just behind try7-opt3, and rosetta likes
try10-opt3.gromacs0.repack-nonPC best.

I think I'm ready to submit:

ReadConformPDB T0440.try9-opt3.pdb	# < dimer/try7-opt3 < try5-opt3 < MQAC1-opt3.gromacs0 < Zhang-Server_TS4
ReadConformPDB T0440.try8-opt3.gromacs0.repack-nonPC.pdb	# < dimer/try6-opt3 < try4-opt3< try2-opt3 < try1-opt3 < align(2yxoA)
ReadConformPDB T0440.try10-opt3.gromacs0.repack-nonPC.pdb	# < MULTICOM-REFINE_TS5
ReadConformPDB T0440.try5-opt3.pdb	# < MQAC1-opt3.gromacs0 < Zhang-Server_TS4
ReadConformPDB T0440.MQAU1-opt3.gromacs0.pdb	# < Zhang-Server_TS4