Kevin Karplus 10 May 1998 T46 seems to be a piece of SW:ADG_MOUSE The target98 method finds no close homologs for t46, and the high scorers 1dfbL and 1obeL are only -3.420 (both immunoglobulins). Using the template models, the top score is for domain 1cid_1, with -3.320. Summing both directions pulls 1tetL to the top with -3.87, along with several other immunoglobulins (mostly having 1nqbA as their FSSP representative, but a few with 8fabA), and has 1cid_1 in second place, with -3.320. The next several hits are all immunoglobulins. The probability of a new fold is approx delta true delta false approx new fold prob domains 55 617 92% fssp-test 18.02 100 85% but if the fold is not new, the best bet is an immunoglobulin light chain, with 1cid as a strong contender. Hmm--1cid has a structural similarity to 1dbjH (an immunoglobulin, though the heavy chain, not the light one). It seems that all the strong hits are saying very roughly the same thing, so they may be worth pursuing, though alignment is going to be tough. -------------------------------------------------- Kevin Karplus 11 May 1998 The 1cid_1 fold is an immunoglobulin also, so all hits are to immunoglobulins. The 1tetL alignments (not using fssp information) look pretty bad--tiny fragments or non-compact regions. Kevin Karplus 26 July 1998 I'm going to remake with the latest Makefile, to see if anything has changed. The remote match to an immunoglobulin is not very encouraging, since the immmunoglobulins are mostly VERY similar (10000 of them only get a total sequence weight of around 40). wu-blast finds nothing (top is 1foh[ABCD] at 0.92) double-blast finds nothing. t46.t98_6 finds 1elt -4.370 5ptp elastase 1lpf[AB] -3.960 3ldaA Dihyrdolipoamide dehydrogenase 1dfbL -3.130 1nqbA immunoglobulin light chain 1obeL -3.130 15 August 1998 Rescored again with newest makefile. Top hits with t46.t98_6 are 2mcm -5.750 2mcm macromycin 1reiA -5.600 1nqbA immunoglobulin 1reiB -5.600 1nqbA 1ar2 -5.450 1nqbA 1tme1 -4.720 2mev1 2mcm now looks most promising. 16 August 1998 Top scorers with fssp-vit library models: 1pbwA -7.080 phosphotransferase 1gdhA -6.590 (Z=2.6 to 4pgaA, 4.3 to 2pia) 1a0p -5.480 4pgaA -5.350 1cid -5.180 (Z=4.7 to 1rsy) 1auuA -5.140 1sxl -5.050 1vjs -4.940 1tc3C -4.890 1rsy -4.190 2pia -4.010 Top scorers with viterbi score on target98 library models: 1cid_1 -9.310 1cid 1cid -7.070 1cid 1aq0A -5.650 1aq0A 8atcB -5.490 8atcB 2polA_3 -5.160 2polA 1ghr -4.820 1aq0A 1mysA_2 -4.640 ? 1aqt -4.570 1aqt 1dar -4.370 1dar I wonder if t46 (gamma-adaptin ear domain) is in any way related to t71 (alpha-adaptin ear domain). Current top alignments (non-self scores) 1cid/1cid-t46-global T0046 119 -9.51 -13.97 1cid/1cid-t46-post T0046 119 -9.51 -13.97 2mcm/t46-2mcm-global 2mcm 112 -8.37 -12.84 2mcm/t46-2mcm-post 2mcm 112 -8.37 -12.84 1pbwA/1pbwA-t46-fssp-global T0046 119 -5.42 -10.36 1cid/1cid-t46-fssp-global T0046 119 -11.04 -10.27 1cid/1cid-t46-vit T0046 119 -8.65 -7.56 1tetL/t46-1tetL-global 1tetL 216 -6.72 -4.49 1tetL/t46-1tetL-post 1tetL 216 -6.72 -4.49 1pbwA/t46-1pbwA-global 1pbwA 184 -4.28 -3.26 1pbwA/t46-1pbwA-post 1pbwA 184 -4.28 -3.26 2mcm/t46-2mcm-vit 2mcm 112 -5.05 -2.99 2mcm/2mcm-t46-global T0046 119 -0.75 -1.37 2mcm/2mcm-t46-post T0046 119 -0.75 -1.37 From karplus@cse.ucsc.edu Sun Aug 16 07:46:36 1998 Return-Path: karplus@cse.ucsc.edu Date: Sun, 16 Aug 1998 07:46:35 -0700 From: Kevin Karplus To: cbarrett@cse.ucsc.edu Cc: karplus@cse.ucsc.edu Subject: t71 and t46 Christian, you gave me papers about the alpha adaptin ear domain (t71). Did you notice that t46 was the gamma adaptin ear domain? Is there any known relationship between these domains? (Do they bind the same things, or totally different things.) From karplus@cse.ucsc.edu Sun Aug 16 12:10:23 1998 Return-Path: karplus@cse.ucsc.edu Date: Sun, 16 Aug 1998 12:10:22 -0700 From: Kevin Karplus To: karplus@cse.ucsc.edu CC: cbarrett@cse.ucsc.edu In-reply-to: <199808161446.HAA09309@purr.cse.ucsc.edu> (message from Kevin Karplus on Sun, 16 Aug 1998 07:46:35 -0700) Subject: Re: t71 and t46 I looked at the paper on adaptin---the GAMMA adaptin ear domain has no homology with the ALPHA adaptin ear domain, and does not bind eps15, so our progress on t71 won't help with t46. 16 August 1998 Top-scorers summing both ways: 1cid_1 -6.490 2mcm -5.750 (1cid Z=4.2) 1rei[AB] -5.600 1ar2 -5.450 1lki -4.98 1tme1 -4.76 1pvc1 -4.72 1lpf[AB] -4.600 Maybe I should take the 1cid-2mcm fssp alignment and use it as a seed for a model? 18 August 1998 I tried building 2mcm-1cid and 1cid-2mcm alignments (in subdirectory 2mcm+1cid). Doing target98 generalization (with constraints) was not successful, because whichever sequence was not chosen as the guide sequence got lost in the target98 process, starting during the first buildmodel. Even though the other sequence remained in the training set (thanks to force_seed) and got high weight (thanks to weight_build), it never survived the buildmodel and realignment process. 19 August 1998 The best summed scores are 1cid_1 -6.490 1cid 2mcm -5.750 2mcm 1reiA -5.600 1nqbA 1reiB -5.600 1nqbA 1ar2 -5.450 1nqbA 1lki -4.98 1lki I modified 1cid-t46-global to get 1cid-t46-hand1, which looks pretty good to me. A smaller modification to 1cid-t46-fssp-global produced 1cid-t46-hand2. Both of these alignments eliminate one sheet of the first beta sandwich, which is a little disturbing. The good scores were all to just the FIRST domain of 1cid. 1cid-t46-hand3 is an attempt to keep the alignment to just the first domain, but I don't think it is very successful. I also modified t46-2mcm-global into t46-2mcm-hand1, which looks better, since it is compact and does not eliminate big chunks of structure. The 1pbwA alignments do not look promising, since 1pbwA is mainly helical, and t46 is predicted to be mainly beta.