Analysis of eteRNA MS2 lab results 2015-01-07 for the improvement of scores in future rounds
By Lars Rose (salish99)
Same State1 Lab - http://eterna.cmu.edu/web/browse/4736272/
First, I have summarized here the shape results graphically to better compare them. At the end of the
table, please see my own conclusions for an improvement on these labs. Feel free to comment / edit /
further these analyses.
User
Name
Given Lab
Condition
Target shapes
Shape State2
Score
comments
100
x
Good hysteresis
mat747
Mat - Mod of Eli
77
Thoughts on MS2 labs 2015-01-07 by salish99
Page 1
Good hysteresis
Eli Fisker
Mod of Meechl's
design Meec..
76
Tesla'sDisci
ple
Ex5 sub 1
75
ElNando88
8
Normal (21/22)
72
lroppy
Same State of
Confusion2
71
Omei
Same State 1 Omei 2
71
Thoughts on MS2 labs 2015-01-07 by salish99
Page 2
machinelve
s
mod of top voted:
#3
69
JR
JR_SameState1_Su
b5
68
Hyphema
Pariah 3 (MS2
Riboswitches ..
68
mat747
Mat - Mod of
Nando
68
Mayanne
Same State #2
67
Good hysteresis
starryjess
Mod of Nando
67
Thoughts on MS2 labs 2015-01-07 by salish99
Page 3
Mayanne
Same State #3
66
Hyphema
Pariah 2 (MS2
Riboswitches ..
66
janetmason Gold Rush
Omei
Same State 1 Omei 3
65
65
SameState1
salish99
Note: Original
shape achieved in
lab
64
Thoughts on MS2 labs 2015-01-07 by salish99
Molecule bound
(-2.51kcal), and
target shape
kept.
As the molecule
is bound in
predicted
shape, there is
no variation on
the fluorescent
signal / NCI.
Bears further
Page 4
thought.
Longer strands
of A’s on right
ring.
Mayanne
salish99
Redo
SameState1NO
62
62
Thoughts on MS2 labs 2015-01-07 by salish99
Mol. bound, but
rest of RNA
diverges from
target shape.
Also no
variation in
fluorescent
levels – FMN
bound as per
lab definition.
Longer strands
of A’s on right
ring.
Page 5
Only very minor
NCI variations
here.
wateronthe
moon
something
completely differ..
janetmason Meow
62
62
lroppy
Same State of
Confusion
60
hoglahoo
Flamingo
59
Thoughts on MS2 labs 2015-01-07 by salish99
Only little
variation on NCI
levels
determined
Longer strands
of A’s on right
ring.
(this seems to
be a correlation
– leave a strand
of A’s to
prevent binding
there into a
different shape
and the NCI
remains lower
across all MS2
concentrations.
Page 6
S
oolong
ss1-2
58
oolong
ss1-3
58
Omei
Same State 1 Omei 1
58
Longer strands
of A’s across
RNA molecule
wateronthe
moon
I 'NO' this state
well 2
57
Meechl
Meechl MS2 SS1 3
56
Thoughts on MS2 labs 2015-01-07 by salish99
Page 7
Longer strands
of A’s across
RNA molecule
wateronthe
moon
hoglahoo
I 'NO' this state
well
GU on the end
56
56
good
“hysteresis”.
A bit of a
surprise that the
overall score is
so low
Longer strands
of A’s across
RNA molecule
eternacac
SameState1-cac2
55
Jieux
Louisiana 1 - Jieux Same ..
53
Thoughts on MS2 labs 2015-01-07 by salish99
Page 8
oolong
ss1
52
Malcolm
SameState1-03
51
Longer strands
of A’s across
RNA molecule
Malcolm
SameState1-02
50
Longer strands
of A’s across
RNA molecule
ViennaUCT
Bexeusisus
50
High foldchange in Kd,obs
jnicol
4736272_48166_2
48
Thoughts on MS2 labs 2015-01-07 by salish99
Page 9
Jieux
Louisiana 2 - Jieux Same ..
47
Longer strands
of A’s across
RNA molecule
eternacac
cipheralex
SameState1-cac1
quick and simple
45
44
Longer strands
of A’s across
RNA molecule
Almost all of the
two loops left as
A’s
Longer strands
of A’s across
RNA molecule
Malcolm
SameState1-01
43
Thoughts on MS2 labs 2015-01-07 by salish99
Page 10
Good hysteresis
(Delta G high
Jieux
Louisiana 3 - Jieux Same ..
42
neo1096
SameState_Neo
41
No variations on the NCI
Ανώνυμος
Αλκαλικός
Same State 1
40
jandersonle
e
Mod of JR
39
machinelve
s
mod of top voted:
#2
37
Thoughts on MS2 labs 2015-01-07 by salish99
Longer strands
of A’s across
RNA molecule.
Almost all of the
two loops left as
A’s
Page 11
jandersonle
e
crooked
36
JR
JR_SameState1_Su
b3
35
mat747
Mat - Mod
35
Eli Fisker
Inspired by JR and
Meechl
34
Tesla'sDisci
ple
Ex5 sub 3
34
Thoughts on MS2 labs 2015-01-07 by salish99
Longer strands
of A’s across
RNA molecule.
Little variation
in NCI
Page 12
lroppy
Same State of
Confusion3 mo..
32
JR
JR_SameState1_Su
b1
30
kawasakiqr
o
Same Satate 1
30
Eli Fisker
Inspired by JR's
SameStare1..
30
Longer strands
of A’s across
RNA molecule
Beginner
Chemist
Default title
30
Thoughts on MS2 labs 2015-01-07 by salish99
Page 13
Meechl
Meechl MS2 SS1 2
30
machinelve
s
mod of top voted:
#1
30
Tesla'sDisci
ple
Ex5 sub 2
30
Longer strands
of A’s across
RNA molecule
jnicol
4736272_48166_3
30
hoglahoo
Mongoose
28
Thoughts on MS2 labs 2015-01-07 by salish99
Page 14
Longer strands
of A’s across
RNA molecule
garydfisher
SS 1.1
27
Hyphema
Pariah 1 (MS2
Riboswitches ..
27
Meechl
Meechl MS2 SS1
22
jnicol
4736272_48166_1
22
janetmason I'm in a state
10
Thoughts on MS2 labs 2015-01-07 by salish99
Page 15
jandersonle
e
Mod of Eli's Mod
6
Not sure is the
formation of the
1-8 hairpin is
the sole reason
for this design
to score that
low? Open for
discussion
A note: I am aware that the delta G calculations as per Johan’s
Is not a true hysteresis (merely a representation of the three sub scores calculated) but I used the term
here when writing together my comments and thoughts in the table above, just in case you wonder
where that terminology comes from.
Ideal: Ending up high on the graph overall, and with a large separation of the two score results.
Thoughts on MS2 labs 2015-01-07 by salish99
Page 16
Findings and conclusions so far
1) Only one design successfully reflected the actual shape required by the lab (Same State 1 by
salsish99)
2) Only two designs (Same State 1 and Same State 1NO by salsish99) had a bound molecule in the
actual lab using the actual FMN docking shape set by the design.
How did those two designs fare?
Their folding score is mediocre at best. The correct shape “Same State 1” also seems to have little fold
change in KD,obs
One conclusion one could draw from this is that achieving the actual desired shape does not result in a
good molecule.
Or, the binding energy provided by the correct FMN docking is insufficient to boost actual binding.
3) Leaving a long set of A’s (I will label these as “stretches of desert”) untouched may result in
desired shapes. Such deserts simply won’t bind well (except maybe to the few U’s strewn
around). However, the overall score of all these molecules is in the lower midrange of all the
submissions analyzed here. So, leaving a maximum of 5 A’s in a row is desirable, if not even less.
4) Maximizing the energy difference between the states seems to result in higher scores, as the
FMN seems to really bind well, even if the target shape does not coincide (even remotely) with
the predetermined binding site. Ultimately, all submissions that were created using this strategy
had a vastly different shape than the one required, but all score better than average, with a
maximum of 80/100.
5) However, high fold-change in Kd,obs alone also does not necessarily result in a good binding site.
Take, for example, 4736272_48166_2 by jnicol, which has a fairly high delta Kd,obs, but scores low
(48). With an average set of values (GC 11 (55%), AU 9 (45%), GU0 (0%), ΔG=-33.5 kcal), this
design also does not fall out of the average submission values. The Tmelt=107 °C is around the
maximum of the submitted designs, so another rule to maximize the score seems to be to keep
the melting point between 67 and 87 °C.
6) Geometric arrangements of non-A’s as in Mod of Eli's Mod by jandersonlee seems to result in
very low folding score and for some reason no differentiation between state energies. So,
another conclusion seems to be to avoid regular arrangements of blocker (i.e. non-A) bases.
Thoughts on MS2 labs 2015-01-07 by salish99
Page 17