%PDF-1.6
%
1 0 obj
<>
endobj
2 0 obj
<>stream
Gregory L. Dignon, Wenwei Zheng, Young C. Kim, Robert B. Best, Jeetain Mittal
Sequence determinants of protein phase behavior from a coarse-grained model
www.ploscompbiol.org
www.ploscompbiol.org
endstream
endobj
3 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 12 0 R/Contents 13 0 R/TrimBox[0 0 612 792]>>
endobj
12 0 obj
[14 0 R 15 0 R 16 0 R 17 0 R 18 0 R 19 0 R 20 0 R 21 0 R 22 0 R 23 0 R 24 0 R 25 0 R 26 0 R 27 0 R 28 0 R 29 0 R 30 0 R 31 0 R 32 0 R 33 0 R 34 0 R 35 0 R 36 0 R 37 0 R 38 0 R 39 0 R 40 0 R 41 0 R 42 0 R 43 0 R 44 0 R 45 0 R 46 0 R 47 0 R 48 0 R 49 0 R 50 0 R 51 0 R 52 0 R 53 0 R 54 0 R 55 0 R 56 0 R 57 0 R 58 0 R 59 0 R 60 0 R 61 0 R 62 0 R 63 0 R 64 0 R 65 0 R 66 0 R 67 0 R]
endobj
14 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref001)>>
endobj
15 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref003)>>
endobj
16 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref004)>>
endobj
17 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref003)>>
endobj
18 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref005)>>
endobj
19 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref007)>>
endobj
20 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref008)>>
endobj
21 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref009)>>
endobj
22 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref010)>>
endobj
23 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref011)>>
endobj
24 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref008)>>
endobj
25 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref012)>>
endobj
26 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref006)>>
endobj
27 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref013)>>
endobj
28 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref014)>>
endobj
29 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref015)>>
endobj
30 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref016)>>
endobj
31 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref017)>>
endobj
32 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref018)>>
endobj
33 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref003)>>
endobj
34 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref019)>>
endobj
35 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref010)>>
endobj
36 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref020)>>
endobj
37 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref022)>>
endobj
38 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref023)>>
endobj
39 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref007)>>
endobj
40 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref015)>>
endobj
41 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref015)>>
endobj
42 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref024)>>
endobj
43 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref025)>>
endobj
44 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref019)>>
endobj
45 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref026)>>
endobj
46 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref027)>>
endobj
47 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref028)>>
endobj
48 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref030)>>
endobj
49 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref002)>>
endobj
50 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref030)>>
endobj
51 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref025)>>
endobj
52 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref028)>>
endobj
53 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref002)>>
endobj
54 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref008)>>
endobj
55 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref025)>>
endobj
56 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref006)>>
endobj
57 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref025)>>
endobj
58 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref031)>>
endobj
59 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref032)>>
endobj
60 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref014)>>
endobj
61 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref033)>>
endobj
62 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref034)>>
endobj
63 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref007)>>
endobj
64 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref015)>>
endobj
65 0 obj
<>/Border[0 0 0]/A 68 0 R>>
endobj
68 0 obj
<>
endobj
66 0 obj
<>/Border[0 0 0]/A 69 0 R>>
endobj
69 0 obj
<>
endobj
67 0 obj
<>/Border[0 0 0]/A 70 0 R>>
endobj
70 0 obj
<>
endobj
13 0 obj
[71 0 R 72 0 R 73 0 R 74 0 R 75 0 R 76 0 R 77 0 R 78 0 R 79 0 R 80 0 R 81 0 R 82 0 R 83 0 R 84 0 R 85 0 R 86 0 R 87 0 R 88 0 R 89 0 R 90 0 R 91 0 R 92 0 R 93 0 R 94 0 R 95 0 R 96 0 R 97 0 R 98 0 R 99 0 R 100 0 R 101 0 R 102 0 R 103 0 R 104 0 R]
endobj
71 0 obj
<>stream
q
0.955 g
0 w
199.9998 713.9999 m
575.9997 713.9999 l
575.9997 514.0003 l
199.9998 514.0003 l
f*
0.83 0.64 0.02 0 k
481.8898 432.9071 m
486.652 432.9071 l
h
f*
491.811 432.9071 m
496.5732 432.9071 l
h
f*
308.0126 419.9244 m
312.7748 419.9244 l
h
f*
383.9811 419.9244 m
388.7433 419.9244 l
h
f*
393.1654 419.9244 m
397.9276 419.9244 l
h
f*
403.1433 419.9244 m
407.8488 419.9244 l
h
f*
493.1717 419.9244 m
497.8772 419.9244 l
h
f*
502.3559 419.9244 m
507.1181 419.9244 l
h
f*
283.011 406.9417 m
292.5354 406.9417 l
h
f*
385.5118 406.9417 m
395.0362 406.9417 l
h
f*
254.6646 380.9197 m
259.4268 380.9197 l
h
f*
263.8488 380.9197 m
273.3732 380.9197 l
h
f*
426.6709 354.8976 m
431.4331 354.8976 l
h
f*
435.9118 354.8976 m
445.3795 354.8976 l
h
f*
449.8583 354.8976 m
459.3827 354.8976 l
h
f*
520.4409 354.8976 m
529.9654 354.8976 l
h
f*
534.3874 354.8976 m
543.9118 354.8976 l
h
f*
304.2142 341.915 m
313.7386 341.915 l
h
f*
318.1606 341.915 m
327.685 341.915 l
h
f*
408.5858 341.915 m
413.348 341.915 l
h
f*
417.7701 341.915 m
427.2945 341.915 l
h
f*
410.0598 328.9323 m
419.5843 328.9323 l
h
f*
424.0063 328.9323 m
433.5307 328.9323 l
h
f*
438.6898 328.9323 m
448.2142 328.9323 l
h
f*
379.7858 315.9496 m
389.3102 315.9496 l
h
f*
491.4142 315.9496 m
496.1197 315.9496 l
h
f*
500.5984 315.9496 m
510.1228 315.9496 l
h
f*
394.1858 289.9276 m
403.7102 289.9276 l
h
f*
408.189 289.9276 m
417.7134 289.9276 l
h
f*
309.5433 237.9402 m
319.0677 237.9402 l
h
f*
203.4142 224.9008 m
212.9386 224.9008 l
h
f*
217.3606 224.9008 m
226.885 224.9008 l
h
f*
461.9339 224.9008 m
471.4016 224.9008 l
h
f*
505.3039 224.9008 m
514.8283 224.9008 l
h
f*
519.9874 224.9008 m
529.5118 224.9008 l
h
f*
203.4142 211.9181 m
208.1764 211.9181 l
h
f*
212.5984 211.9181 m
222.1228 211.9181 l
h
f*
235.4457 198.9354 m
244.9701 198.9354 l
h
f*
342.7654 198.9354 m
352.2331 198.9354 l
h
f*
323.9433 185.8961 m
328.7055 185.8961 l
h
f*
333.1276 185.8961 m
337.8898 185.8961 l
h
f*
342.3685 185.8961 m
351.8929 185.8961 l
h
f*
521.8583 172.9134 m
526.6205 172.9134 l
h
f*
531.0425 172.9134 m
540.5669 172.9134 l
h
f*
545.0457 172.9134 m
554.5134 172.9134 l
h
f*
500.0882 159.9307 m
509.6126 159.9307 l
h
f*
468.0567 146.948 m
477.5811 146.948 l
h
f*
492.378 133.9087 m
501.9024 133.9087 l
h
f*
474.5764 120.926 m
484.1008 120.926 l
h
f*
451.6724 107.9433 m
456.4346 107.9433 l
h
f*
460.9134 107.9433 m
470.4378 107.9433 l
h
f*
0 g
1 j
1 J
11.9999 0 0 11.9999 209.9905 696.0188 cm
BT
/F0 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Author)Tj
3.137 0 Td
(summary)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 209.9905 677.9905 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Liquid)Tj
2.8573 0 Td
(liquid)Tj
2.5625 0 Td
(phase)Tj
2.4831 0 Td
(separation)Tj
4.3823 0 Td
(\(LLPS\))Tj
3.0104 0 Td
(of)Tj
1.0148 0 Td
(low-complexity)Tj
6.4289 0 Td
(protein)Tj
3.1521 0 Td
(sequences)Tj
4.2236 0 Td
(has)Tj
1.5421 0 Td
(emerged)Tj
-31.6571 -1.2982 Td
(as)Tj
1.0147 0 Td
(an)Tj
1.2019 0 Td
(important)Tj
4.286 0 Td
(research)Tj
3.5546 0 Td
(topic)Tj
2.2337 0 Td
(due)Tj
1.6951 0 Td
(to)Tj
1.0261 0 Td
(its)Tj
1.1452 0 Td
(relevance)Tj
3.9685 0 Td
(to)Tj
1.0261 0 Td
(membraneless)Tj
5.9584 0 Td
(organelles)Tj
4.2463 0 Td
(and)Tj
1.7348 0 Td
(intra-)Tj
-33.0914 -1.2983 Td
(cellular)Tj
3.1407 0 Td
(compartmentalization.)Tj
9.3203 0 Td
(However)Tj
3.8494 0 Td
(a)Tj
0.6576 0 Td
(molecular)Tj
4.218 0 Td
(level)Tj
2.0125 0 Td
(understanding)Tj
6.0718 0 Td
(of)Tj
1.0148 0 Td
(LLPS)Tj
2.3301 0 Td
(cannot)Tj
-32.6152 -1.3039 Td
(be)Tj
1.1508 0 Td
(easily)Tj
2.4094 0 Td
(obtained)Tj
3.7304 0 Td
(by)Tj
1.1792 0 Td
(experimental)Tj
5.4595 0 Td
(methods)Tj
3.685 0 Td
(due)Tj
1.7008 0 Td
(to)Tj
1.0261 0 Td
(difficulty)Tj
3.8098 0 Td
(of)Tj
1.0148 0 Td
(determining)Tj
5.176 0 Td
(structural)Tj
-30.3418 -1.2983 Td
(properties)Tj
4.2802 0 Td
(of)Tj
1.0148 0 Td
(phase)Tj
2.4832 0 Td
(separated)Tj
4.0081 0 Td
(protein)Tj
3.1521 0 Td
(assemblies,)Tj
4.6488 0 Td
(and)Tj
1.7348 0 Td
(of)Tj
1.0148 0 Td
(choosing)Tj
3.8268 0 Td
(appropriate)Tj
4.8755 0 Td
(mutations.)Tj
-31.0391 -1.2982 Td
(Here)Tj
2.2053 0 Td
(we)Tj
1.3266 0 Td
(advance)Tj
3.4696 0 Td
(a)Tj
0.6519 0 Td
(coarse-grained)Tj
6.1285 0 Td
(computational)Tj
6.0491 0 Td
(framework)Tj
4.6148 0 Td
(for)Tj
1.3889 0 Td
(accessing)Tj
3.9232 0 Td
(the)Tj
1.474 0 Td
(long)Tj
1.9842 0 Td
(time)Tj
-33.2161 -1.3039 Td
(scale)Tj
2.1089 0 Td
(phase)Tj
2.4831 0 Td
(separation)Tj
4.3824 0 Td
(process)Tj
3.1861 0 Td
(and)Tj
1.7291 0 Td
(for)Tj
1.3833 0 Td
(obtaining)Tj
4.0649 0 Td
(molecular)Tj
4.2179 0 Td
(details)Tj
2.7779 0 Td
(of)Tj
1.0148 0 Td
(LLPS,)Tj
2.5569 0 Td
(in)Tj
1.0374 0 Td
(conjunction)Tj
-30.9427 -1.2983 Td
(with)Tj
1.9955 0 Td
(state)Tj
2.0353 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(art)Tj
1.3209 0 Td
(enhanced)Tj
4.0762 0 Td
(sampling)Tj
3.8835 0 Td
(methods.)Tj
3.9061 0 Td
(We)Tj
1.6101 0 Td
(are)Tj
1.4513 0 Td
(able)Tj
1.8312 0 Td
(to)Tj
1.0204 0 Td
(qualitatively)Tj
5.0797 0 Td
(capture)Tj
3.2144 0 Td
(the)Tj
-33.9134 -1.2983 Td
(changes)Tj
3.4015 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.474 0 Td
(phase)Tj
2.4831 0 Td
(diagram)Tj
3.5377 0 Td
(due)Tj
1.7007 0 Td
(to)Tj
1.0262 0 Td
(specific)Tj
3.1861 0 Td
(mutations,)Tj
4.507 0 Td
(inclusion)Tj
3.9175 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.6576 0 Td
(folded)Tj
2.7383 0 Td
(domain,)Tj
3.5489 0 Td
(and)Tj
-34.2082 -1.3039 Td
(variation)Tj
3.804 0 Td
(of)Tj
1.0148 0 Td
(chain)Tj
2.4208 0 Td
(length.)Tj
2.9537 0 Td
(The)Tj
1.7801 0 Td
(model)Tj
2.7439 0 Td
(is)Tj
0.8504 0 Td
(flexible)Tj
3.0898 0 Td
(and)Tj
1.7291 0 Td
(can)Tj
1.6271 0 Td
(be)Tj
1.1452 0 Td
(used)Tj
2.0636 0 Td
(with)Tj
1.9955 0 Td
(different)Tj
3.6567 0 Td
(knowledge-)Tj
-30.8747 -1.2983 Td
(based)Tj
2.4717 0 Td
(potential)Tj
3.7644 0 Td
(energy)Tj
2.9027 0 Td
(functions,)Tj
4.2179 0 Td
(as)Tj
1.0148 0 Td
(we)Tj
1.3266 0 Td
(demonstrate.)Tj
5.4595 0 Td
(We)Tj
1.6101 0 Td
(expect)Tj
2.7722 0 Td
(a)Tj
0.652 0 Td
(wide)Tj
2.1203 0 Td
(application)Tj
4.6828 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-34.0098 -1.2982 Td
(presented)Tj
4.1158 0 Td
(framework)Tj
4.6148 0 Td
(for)Tj
1.389 0 Td
(advancing)Tj
4.3199 0 Td
(our)Tj
1.6271 0 Td
(understanding)Tj
6.0718 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(formation)Tj
4.2576 0 Td
(of)Tj
1.0148 0 Td
(liquid-like)Tj
-29.8939 -1.2983 Td
(protein)Tj
3.1521 0 Td
(assemblies.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 477.0141 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Introduction)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 460.0062 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(Intracellular)Tj
5.1306 0 Td
(compartmentalization)Tj
9.0935 0 Td
(is)Tj
0.8504 0 Td
(essential)Tj
3.583 0 Td
(for)Tj
1.3833 0 Td
(normal)Tj
3.1521 0 Td
(physiological)Tj
5.4425 0 Td
(activity.)Tj
3.3392 0 Td
(This)Tj
1.9899 0 Td
(is)Tj
-33.9645 -1.2982 Td
(commonly)Tj
4.5467 0 Td
(accomplished)Tj
5.6976 0 Td
(through)Tj
3.4412 0 Td
(isolation)Tj
3.6567 0 Td
(by)Tj
1.1849 0 Td
(lipid)Tj
2.0466 0 Td
(membranes)Tj
4.9266 0 Td
(or)Tj
1.0998 0 Td
(vesicles,)Tj
3.4016 0 Td
(but)Tj
1.5533 0 Td
(can)Tj
1.6271 0 Td
(also)Tj
1.7688 0 Td
(be)Tj
-34.9509 -1.3039 Td
(achieved)Tj
3.702 0 Td
(without)Tj
3.3278 0 Td
(the)Tj
1.4684 0 Td
(use)Tj
1.5363 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(membrane)Tj
4.5694 0 Td
(via)Tj
1.372 0 Td
(membraneless)Tj
5.9584 0 Td
(organelles)Tj
4.2462 0 Td
([)Tj
0.83 0.64 0.02 0 k
(1)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(].)Tj
2.5966 0 Td
(These)Tj
2.5681 0 Td
(organelles)Tj
-33.012 -1.2983 Td
(include)Tj
3.1804 0 Td
(processing)Tj
4.4674 0 Td
(bodies)Tj
2.8119 0 Td
([)Tj
0.83 0.64 0.02 0 k
(4)Tj
0 g
(],)Tj
1.6044 0 Td
(stress)Tj
2.3925 0 Td
(granules)Tj
3.5999 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(5)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(])Tj
2.0296 0 Td
(and)Tj
1.7291 0 Td
(germ)Tj
2.3017 0 Td
(granules)Tj
3.6 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(9)Tj
0 g
(])Tj
1.0375 0 Td
(in)Tj
1.0318 0 Td
(the)Tj
1.474 0 Td
(cyto-)Tj
-33.7774 -1.2983 Td
(plasm,)Tj
2.8232 0 Td
(and)Tj
1.7292 0 Td
(nucleoli)Tj
3.4072 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(])Tj
1.8538 0 Td
(and)Tj
1.7292 0 Td
(nuclear)Tj
3.1974 0 Td
(speckles)Tj
3.4696 0 Td
([)Tj
0.83 0.64 0.02 0 k
(11)Tj
0 g
(])Tj
1.8538 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4684 0 Td
(nucleus.)Tj
3.5036 0 Td
(It)Tj
0.856 0 Td
(has)Tj
1.5421 0 Td
(recently)Tj
3.4128 0 Td
(been)Tj
2.1203 0 Td
(estab-)Tj
-34.0041 -1.3039 Td
(lished)Tj
2.5738 0 Td
(that)Tj
1.7745 0 Td
(many)Tj
2.4774 0 Td
(of)Tj
1.0148 0 Td
(these)Tj
2.2564 0 Td
(membraneless)Tj
5.9584 0 Td
(organelles)Tj
4.2463 0 Td
(can)Tj
1.627 0 Td
(be)Tj
1.1509 0 Td
(described)Tj
4.0478 0 Td
(as)Tj
1.0148 0 Td
(phase)Tj
2.4888 0 Td
(separated)Tj
4.0082 0 Td
(liquid-)Tj
-34.6391 -1.2982 Td
(like)Tj
1.6497 0 Td
(droplets)Tj
3.4753 0 Td
([)Tj
0.83 0.64 0.02 0 k
(8)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2585 0 Td
(12)Tj
0 g
(].)Tj
1.7405 0 Td
(The)Tj
1.7801 0 Td
(process)Tj
3.1862 0 Td
(of)Tj
1.0148 0 Td
(liquid-liquid)Tj
5.2554 0 Td
(phase)Tj
2.4831 0 Td
(separation)Tj
4.3823 0 Td
(\(LLPS\))Tj
3.0104 0 Td
(allows)Tj
2.6986 0 Td
(these)Tj
2.2563 0 Td
(organ-)Tj
-34.1912 -1.2983 Td
(elles)Tj
1.9218 0 Td
(to)Tj
1.0205 0 Td
(spontaneously)Tj
5.9584 0 Td
(coalesce)Tj
3.4582 0 Td
(and)Tj
1.7348 0 Td
(disperse,)Tj
3.6964 0 Td
(and)Tj
1.7291 0 Td
(is)Tj
0.8504 0 Td
(important)Tj
4.2803 0 Td
(for)Tj
1.3833 0 Td
(many)Tj
2.4774 0 Td
(biological)Tj
4.0932 0 Td
(functions,)Tj
-32.6038 -1.3039 Td
(such)Tj
2.0579 0 Td
(as)Tj
1.0148 0 Td
(response)Tj
3.736 0 Td
(to)Tj
1.0205 0 Td
(heat)Tj
1.9049 0 Td
(shock)Tj
2.5341 0 Td
(and)Tj
1.7348 0 Td
(other)Tj
2.3471 0 Td
(forms)Tj
2.5682 0 Td
(of)Tj
1.0148 0 Td
(stress)Tj
2.3924 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2642 0 Td
(13)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.3947 0 Td
(14)Tj
0 g
(],)Tj
1.7348 0 Td
(DNA)Tj
2.381 0 Td
(repair)Tj
2.6022 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(16)Tj
0 g
(],)Tj
1.7405 0 Td
(regu-)Tj
-35.1777 -1.2983 Td
(lation)Tj
2.5171 0 Td
(of)Tj
1.0148 0 Td
(gene)Tj
2.0863 0 Td
(expression)Tj
4.4617 0 Td
([)Tj
0.83 0.64 0.02 0 k
(17)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(18)Tj
0 g
(],)Tj
1.7404 0 Td
(cellular)Tj
3.1351 0 Td
(signaling)Tj
3.8268 0 Td
([)Tj
0.83 0.64 0.02 0 k
(3)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(19)Tj
0 g
(],)Tj
1.7404 0 Td
(and)Tj
1.7291 0 Td
(many)Tj
2.4775 0 Td
(other)Tj
2.3471 0 Td
(functions)Tj
3.9911 0 Td
(requir-)Tj
-34.0608 -1.2983 Td
(ing)Tj
1.5023 0 Td
(spatial)Tj
2.7723 0 Td
(organization)Tj
5.2837 0 Td
(and)Tj
1.7291 0 Td
(biochemical)Tj
5.0684 0 Td
(regulation)Tj
4.3086 0 Td
([)Tj
0.83 0.64 0.02 0 k
(10)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(20)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(22)Tj
0 g
(].)Tj
3.2088 0 Td
(LLPS)Tj
2.33 0 Td
(has)Tj
1.5421 0 Td
(also)Tj
1.7688 0 Td
(been)Tj
2.1203 0 Td
(implicated)Tj
-33.3692 -1.2982 Td
(as)Tj
1.0147 0 Td
(a)Tj
0.652 0 Td
(precursor)Tj
4.0932 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4684 0 Td
(formation)Tj
4.2633 0 Td
(of)Tj
1.0148 0 Td
(hydrogels)Tj
4.1045 0 Td
([)Tj
0.83 0.64 0.02 0 k
(23)Tj
0 g
(])Tj
1.8482 0 Td
(and)Tj
1.7348 0 Td
(fibrillar)Tj
3.2144 0 Td
(aggregates)Tj
4.3654 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2585 0 Td
(15)Tj
0 g
(],)Tj
1.7348 0 Td
(suggesting)Tj
-31.7931 -1.3039 Td
(possible)Tj
3.4072 0 Td
(relevance)Tj
3.9685 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4683 0 Td
(pathogenesis)Tj
5.3575 0 Td
(of)Tj
1.0148 0 Td
(many)Tj
2.4774 0 Td
(diseases)Tj
3.3789 0 Td
(including)Tj
4.0422 0 Td
(Amyotrophic)Tj
5.5955 0 Td
(Lateral)Tj
2.9651 0 Td
(Sclero-)Tj
-34.7015 -1.2983 Td
(sis)Tj
1.2075 0 Td
(\(ALS\))Tj
2.5965 0 Td
(and)Tj
1.7348 0 Td
(Frontotemporal)Tj
6.5934 0 Td
(Dementia)Tj
4.1725 0 Td
(\(FTD\))Tj
2.7723 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7405 0 Td
(24)Tj
0 g
(].)Tj
-19.6213 -1.2983 Td
(Experimental)Tj
5.6069 0 Td
(studies)Tj
2.9877 0 Td
(have)Tj
2.0579 0 Td
(characterized)Tj
5.5615 0 Td
(different)Tj
3.651 0 Td
(properties)Tj
4.2803 0 Td
(of)Tj
1.0148 0 Td
(biological)Tj
4.0876 0 Td
(LLPS,)Tj
2.5568 0 Td
(and)Tj
1.7348 0 Td
(have)Tj
-34.7355 -1.3039 Td
(shown)Tj
2.8459 0 Td
(that)Tj
1.7802 0 Td
(many)Tj
2.4774 0 Td
(systems)Tj
3.2995 0 Td
(share)Tj
2.3358 0 Td
(several)Tj
2.9366 0 Td
(common)Tj
3.8438 0 Td
(characteristics.)Tj
6.1285 0 Td
(First,)Tj
2.2733 0 Td
(the)Tj
1.4684 0 Td
(formation)Tj
4.2633 0 Td
(and)Tj
1.7291 0 Td
(dis-)Tj
-35.3818 -1.2982 Td
(solution)Tj
3.4809 0 Td
(processes)Tj
3.9685 0 Td
(can)Tj
1.627 0 Td
(be)Tj
1.1509 0 Td
(tuned)Tj
2.5455 0 Td
(by)Tj
1.1792 0 Td
(the)Tj
1.474 0 Td
(cellular)Tj
3.1351 0 Td
(environment)Tj
5.4311 0 Td
(such)Tj
2.0636 0 Td
(as)Tj
1.0148 0 Td
(changes)Tj
3.4016 0 Td
(in)Tj
1.0375 0 Td
(temperature,)Tj
-31.5097 -1.2983 Td
(pH)Tj
1.5023 0 Td
(and)Tj
1.7291 0 Td
(salt)Tj
1.5647 0 Td
(concentration)Tj
5.8167 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(],)Tj
2.0749 0 Td
(by)Tj
1.1849 0 Td
(post-translational)Tj
7.2453 0 Td
(modification)Tj
5.3745 0 Td
(such)Tj
2.0636 0 Td
(as)Tj
1.0148 0 Td
(phosphorylation)Tj
-29.5708 -1.3039 Td
([)Tj
0.83 0.64 0.02 0 k
(19)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7347 0 Td
(26)Tj
0 g
(],)Tj
1.7348 0 Td
(and)Tj
1.7348 0 Td
(by)Tj
1.1792 0 Td
(mixing)Tj
3.0558 0 Td
(with)Tj
1.9955 0 Td
(other)Tj
2.3471 0 Td
(biomolecules)Tj
5.4765 0 Td
(such)Tj
2.0636 0 Td
(as)Tj
1.0148 0 Td
(proteins)Tj
3.515 0 Td
([)Tj
0.83 0.64 0.02 0 k
(27)Tj
0 g
(],)Tj
2.0749 0 Td
(RNA)Tj
2.262 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
()Tj
0.83 0.64 0.02 0 k
(30)Tj
0 g
(],)Tj
3.5433 0 Td
(and)Tj
1.7348 0 Td
(ATP)Tj
-35.4668 -1.2983 Td
([)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2585 0 Td
(30)Tj
0 g
(].)Tj
1.7405 0 Td
(Second,)Tj
3.3505 0 Td
(the)Tj
1.4684 0 Td
(concentrated)Tj
5.4481 0 Td
(phase)Tj
2.4831 0 Td
(has)Tj
1.5421 0 Td
(liquid-like)Tj
4.3483 0 Td
(properties,)Tj
4.5014 0 Td
(including)Tj
4.0422 0 Td
(fusion,)Tj
2.9423 0 Td
(dripping,)Tj
-33.1254 -1.2983 Td
(wetting)Tj
3.2031 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(])Tj
1.8538 0 Td
(and)Tj
1.7291 0 Td
(Ostwald)Tj
3.515 0 Td
(ripening)Tj
3.634 0 Td
([)Tj
0.83 0.64 0.02 0 k
(28)Tj
0 g
(],)Tj
2.0749 0 Td
(and)Tj
1.7292 0 Td
(its)Tj
1.1451 0 Td
(viscosity)Tj
3.617 0 Td
(is)Tj
0.8447 0 Td
(typically)Tj
3.566 0 Td
(several)Tj
2.931 0 Td
(orders)Tj
2.7836 0 Td
(of)Tj
1.0148 0 Td
(magni-)Tj
-33.6413 -1.3039 Td
(tude)Tj
1.9955 0 Td
(higher)Tj
2.8006 0 Td
(than)Tj
2.0296 0 Td
(that)Tj
1.7802 0 Td
(of)Tj
1.0148 0 Td
(water)Tj
2.4321 0 Td
([)Tj
0.83 0.64 0.02 0 k
(2)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(8)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
0.9241 0 Td
(25)Tj
0 g
(].)Tj
1.7347 0 Td
(Third,)Tj
2.7496 0 Td
(LLPS)Tj
2.3301 0 Td
(is)Tj
0.8504 0 Td
(commonly)Tj
4.5467 0 Td
(driven)Tj
2.812 0 Td
(or)Tj
1.0998 0 Td
(modulated)Tj
4.5297 0 Td
(by)Tj
1.1849 0 Td
(low)Tj
-36.0734 -1.2982 Td
(complexity)Tj
4.6431 0 Td
(\(LC\))Tj
2.0976 0 Td
(intrinsically)Tj
4.9549 0 Td
(disordered)Tj
4.5298 0 Td
(regions)Tj
3.1634 0 Td
(\(IDRs\))Tj
2.9594 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(protein)Tj
3.1521 0 Td
(sequence)Tj
3.8608 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2585 0 Td
(25)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.4003 0 Td
(31)Tj
0 g
(],)Tj
-34.503 -1.2983 Td
(suggesting)Tj
4.3993 0 Td
(similarities)Tj
4.6034 0 Td
(to)Tj
1.0262 0 Td
(the)Tj
1.4683 0 Td
(well-characterized)Tj
7.5118 0 Td
(LLPS)Tj
2.33 0 Td
(of)Tj
1.0148 0 Td
(polymer)Tj
3.5603 0 Td
(mixtures)Tj
3.7531 0 Td
([)Tj
0.83 0.64 0.02 0 k
(32)Tj
0 g
(].)Tj
2.0806 0 Td
(It)Tj
0.856 0 Td
(should)Tj
2.9197 0 Td
(be)Tj
-35.5235 -1.2983 Td
(noted)Tj
2.5228 0 Td
(that)Tj
1.7801 0 Td
(a)Tj
0.652 0 Td
(disordered)Tj
4.5297 0 Td
(domain)Tj
3.3222 0 Td
(is)Tj
0.8504 0 Td
(not)Tj
1.5704 0 Td
(necessary)Tj
4.0251 0 Td
(for)Tj
1.3833 0 Td
(LLPS)Tj
2.3301 0 Td
(to)Tj
1.0261 0 Td
(occur)Tj
2.4718 0 Td
([)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
(],)Tj
2.0807 0 Td
(and)Tj
1.7291 0 Td
(indeed)Tj
2.9366 0 Td
(LLPS)Tj
2.3301 0 Td
(is)Tj
-35.5405 -1.3039 Td
(known)Tj
3.0047 0 Td
(to)Tj
1.0261 0 Td
(occur)Tj
2.4718 0 Td
(for)Tj
1.3833 0 Td
(folded)Tj
2.7439 0 Td
(proteins)Tj
3.5149 0 Td
(during)Tj
2.9254 0 Td
(crystallization)Tj
5.7883 0 Td
(or)Tj
1.0998 0 Td
(purification)Tj
4.9379 0 Td
([)Tj
0.83 0.64 0.02 0 k
(33)Tj
0 g
(].)Tj
2.075 0 Td
(Folded)Tj
2.982 0 Td
(domains)Tj
-33.9531 -1.2983 Td
(along)Tj
2.4207 0 Td
(with)Tj
1.9956 0 Td
(IDRs)Tj
2.2734 0 Td
(have)Tj
2.0636 0 Td
(also)Tj
1.7631 0 Td
(been)Tj
2.1203 0 Td
(shown)Tj
2.8517 0 Td
(to)Tj
1.0204 0 Td
(modulate)Tj
4.0025 0 Td
(LLPS)Tj
2.3301 0 Td
(properties)Tj
4.2746 0 Td
([)Tj
0.83 0.64 0.02 0 k
(34)Tj
0 g
(].)Tj
2.0806 0 Td
(Lastly,)Tj
2.7723 0 Td
(some)Tj
2.33 0 Td
(proteins)Tj
-34.2989 -1.2982 Td
(involved)Tj
3.651 0 Td
(in)Tj
1.0318 0 Td
(LLPS)Tj
2.33 0 Td
(process)Tj
3.1861 0 Td
(are)Tj
1.4514 0 Td
(also)Tj
1.7631 0 Td
(able)Tj
1.8312 0 Td
(to)Tj
1.0261 0 Td
(form)Tj
2.2054 0 Td
(fibril)Tj
2.1656 0 Td
(structures)Tj
4.1839 0 Td
([)Tj
0.83 0.64 0.02 0 k
(7)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2643 0 Td
(15)Tj
0 g
(],)Tj
1.7348 0 Td
(suggesting)Tj
4.405 0 Td
(a)Tj
0.6519 0 Td
(possible)Tj
-32.8816 -1.3039 Td
(connection)Tj
4.7168 0 Td
(between)Tj
3.5262 0 Td
(the)Tj
1.4684 0 Td
(liquid-like)Tj
4.3483 0 Td
(droplet)Tj
3.1124 0 Td
(and)Tj
1.7291 0 Td
(solid)Tj
2.126 0 Td
(fibril)Tj
2.1713 0 Td
(states.)Tj
2.6192 0 Td
(However,)Tj
4.0762 0 Td
(the)Tj
1.4684 0 Td
(molecular)Tj
4.2236 0 Td
(level)Tj
-35.5859 -1.2983 Td
(understanding)Tj
6.0661 0 Td
(of)Tj
1.0148 0 Td
(LLPS)Tj
2.3357 0 Td
(cannot)Tj
2.9763 0 Td
(be)Tj
1.1509 0 Td
(easily)Tj
2.4094 0 Td
(obtained)Tj
3.7304 0 Td
(by)Tj
1.1792 0 Td
(experimental)Tj
5.4595 0 Td
(methods)Tj
3.685 0 Td
(due)Tj
1.7008 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 169.285 23.6976 re
W* n
q
169.2283 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 356.9385 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Sequenc)Tj
3.8764 0 Td
(e)Tj
0.7653 0 Td
(determinants)Tj
5.9032 0 Td
(of)Tj
1.0418 0 Td
(protein)Tj
3.2173 0 Td
(liquid-liqu)Tj
4.1174 0 Td
(id)Tj
0.9779 0 Td
(phase)Tj
2.8985 0 Td
(separati)Tj
3.4866 0 Td
(on)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
142.5827 34.9228 m
295.8236 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(Computationa)Tj
6.1229 0 Td
(l)Tj
0.4322 0 Td
(Biology)Tj
3.4371 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https:/)Tj
2.6788 0 Td
(/doi.org/10.13)Tj
6.0094 0 Td
(71/journal.p)Tj
5.1166 0 Td
(cbi.1005941)Tj
0 g
6.3497 0 Td
(January)Tj
3.7134 0 Td
(24,)Tj
1.5874 0 Td
(2018)Tj
26.3624 0 Td
(2)Tj
0.7654 0 Td
(/)Tj
0.496 0 Td
(23)Tj
ET
Q
q
0.83 0.64 0.02 0 k
1 j
1 J
0 w
161.6882 630.652 m
179.4331 630.652 l
h
f*
36 619.6535 m
70.5827 619.6535 l
h
f*
0 g
7.9999 0 0 7.9999 36 708.7181 cm
BT
/F10 1 Tf
1 TL
-0.025 Tc
0 0 Td
(which)Tj
2.4236 0 Td
(is)Tj
0.8291 0 Td
(supported)Tj
3.9969 0 Td
(by)Tj
1.1126 0 Td
(the)Tj
1.3677 0 Td
(National)Tj
3.2387 0 Td
(Science)Tj
-12.9686 -1.3748 Td
(Foundation,)Tj
4.5779 0 Td
(project)Tj
2.7638 0 Td
(no.)Tj
1.389 0 Td
(TG-MCB120)Tj
4.5922 0 Td
(014,)Tj
1.8638 0 Td
(is)Tj
0.8362 0 Td
(also)Tj
-16.0229 -1.3748 Td
(gratefully)Tj
3.6354 0 Td
(acknowledge)Tj
4.8331 0 Td
(d.)Tj
0.9213 0 Td
(R.B.)Tj
1.7787 0 Td
(and)Tj
1.5875 0 Td
(W.Z.)Tj
1.9488 0 Td
(were)Tj
-14.7048 -1.3748 Td
(supported)Tj
3.9897 0 Td
(by)Tj
1.1197 0 Td
(the)Tj
1.3678 0 Td
(Intramural)Tj
4.0819 0 Td
(Research)Tj
3.6992 0 Td
(Progra)Tj
2.5016 0 Td
(m)Tj
0.978 0 Td
(of)Tj
-17.7379 -1.3748 Td
(the)Tj
1.3677 0 Td
(National)Tj
3.2386 0 Td
(Institute)Tj
3.2244 0 Td
(of)Tj
0.9496 0 Td
(Diabetes)Tj
3.4158 0 Td
(and)Tj
1.5874 0 Td
(Digestive)Tj
3.6071 0 Td
(and)Tj
-17.3906 -1.3748 Td
(Kidney)Tj
2.7283 0 Td
(Diseases)Tj
3.5292 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
1.3677 0 Td
(National)Tj
3.2386 0 Td
(Institutes)Tj
3.6497 0 Td
(of)Tj
-15.4631 -1.3748 Td
(Health.)Tj
2.7992 0 Td
(This)Tj
1.7787 0 Td
(work)Tj
2.0623 0 Td
(utilized)Tj
2.7779 0 Td
(the)Tj
1.3748 0 Td
(computation)Tj
4.6631 0 Td
(al)Tj
-15.456 -1.3748 Td
(resources)Tj
3.8905 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
1.3678 0 Td
(NIH)Tj
1.6512 0 Td
(HPC)Tj
1.8567 0 Td
(Biowulf)Tj
2.9764 0 Td
(cluster)Tj
2.7142 0 Td
(\()Tj
0.83 0.64 0.02 0 k
(http://)Tj
-15.4064 -1.3749 Td
(hpc.nih.gov)Tj
0 g
4.3228 0 Td
(\).)Tj
0.7512 0 Td
(The)Tj
1.5874 0 Td
(funders)Tj
3.0473 0 Td
(had)Tj
1.5874 0 Td
(no)Tj
1.1693 0 Td
(role)Tj
1.6158 0 Td
(in)Tj
0.8858 0 Td
(study)Tj
-14.967 -1.3748 Td
(design,)Tj
2.8984 0 Td
(data)Tj
1.7929 0 Td
(collection)Tj
3.7418 0 Td
(and)Tj
1.5874 0 Td
(analysis,)Tj
3.4087 0 Td
(decision)Tj
3.2953 0 Td
(to)Tj
-16.7245 -1.3748 Td
(publish,)Tj
3.1464 0 Td
(or)Tj
0.9993 0 Td
(preparation)Tj
4.4433 0 Td
(of)Tj
0.9496 0 Td
(the)Tj
1.3677 0 Td
(manuscript.)Tj
/F9 1 Tf
-10.9063 -2.126 Td
(Competing)Tj
4.3795 0 Td
(interests)Tj
3.3307 0 Td
(:)Tj
/F10 1 Tf
0.4819 0 Td
(The)Tj
1.5875 0 Td
(authors)Tj
3.0401 0 Td
(have)Tj
1.963 0 Td
(declared)Tj
-14.7827 -1.3748 Td
(that)Tj
1.6228 0 Td
(no)Tj
1.1693 0 Td
(competing)Tj
4.1599 0 Td
(interests)Tj
ET
endstream
endobj
72 0 obj
<>stream
endstream
endobj
73 0 obj
<>stream
endstream
endobj
74 0 obj
<>stream
endstream
endobj
75 0 obj
<>stream
endstream
endobj
76 0 obj
<>stream
endstream
endobj
77 0 obj
<>stream
endstream
endobj
78 0 obj
<>stream
endstream
endobj
79 0 obj
<>stream
endstream
endobj
80 0 obj
<>stream
endstream
endobj
81 0 obj
<>stream
endstream
endobj
82 0 obj
<>stream
endstream
endobj
83 0 obj
<>stream
endstream
endobj
84 0 obj
<>stream
endstream
endobj
85 0 obj
<>stream
endstream
endobj
86 0 obj
<>stream
endstream
endobj
87 0 obj
<>stream
endstream
endobj
88 0 obj
<>stream
endstream
endobj
89 0 obj
<>stream
endstream
endobj
90 0 obj
<>stream
endstream
endobj
91 0 obj
<>stream
endstream
endobj
92 0 obj
<>stream
endstream
endobj
93 0 obj
<>stream
endstream
endobj
94 0 obj
<>stream
endstream
endobj
95 0 obj
<>stream
endstream
endobj
96 0 obj
<>stream
endstream
endobj
97 0 obj
<>stream
endstream
endobj
98 0 obj
<>stream
endstream
endobj
99 0 obj
<>stream
endstream
endobj
100 0 obj
<>stream
endstream
endobj
101 0 obj
<>stream
endstream
endobj
102 0 obj
<>stream
endstream
endobj
103 0 obj
<>stream
endstream
endobj
104 0 obj
<>stream
BT
10.3394 -17.2489 Td
(exist.)Tj
ET
Q
endstream
endobj
105 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 108 0 R/Contents 109 0 R/TrimBox[0 0 612 792]>>
endobj
108 0 obj
[110 0 R 111 0 R 112 0 R 113 0 R 114 0 R 115 0 R 116 0 R 117 0 R 118 0 R 119 0 R 120 0 R 121 0 R 122 0 R 123 0 R 124 0 R 125 0 R 126 0 R 127 0 R 128 0 R 129 0 R 130 0 R 131 0 R 132 0 R]
endobj
110 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref006)>>
endobj
111 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref035)>>
endobj
112 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref036)>>
endobj
113 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref037)>>
endobj
114 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref038)>>
endobj
115 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref039)>>
endobj
116 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref014)>>
endobj
117 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref040)>>
endobj
118 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref041)>>
endobj
119 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref042)>>
endobj
120 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref043)>>
endobj
121 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref044)>>
endobj
122 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref045)>>
endobj
123 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref046)>>
endobj
124 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref047)>>
endobj
125 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref006)>>
endobj
126 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref015)>>
endobj
127 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref025)>>
endobj
128 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref048)>>
endobj
129 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref049)>>
endobj
130 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref015)>>
endobj
131 0 obj
<>/Border[0 0 0]/Dest(Rpcbi.1005941.ref025)>>
endobj
132 0 obj
<>/Border[0 0 0]/A 133 0 R>>
endobj
133 0 obj
<>
endobj
109 0 obj
[134 0 R 135 0 R 136 0 R 137 0 R 138 0 R 139 0 R 140 0 R 141 0 R 142 0 R 143 0 R 144 0 R 145 0 R 146 0 R 147 0 R 148 0 R 149 0 R 150 0 R 151 0 R 152 0 R 153 0 R 154 0 R 155 0 R]
endobj
134 0 obj
<>stream
q
0.83 0.64 0.02 0 k
500.8819 706.337 m
505.6441 706.337 l
h
f*
365.0457 693.2976 m
374.5701 693.2976 l
h
f*
457.5685 641.3102 m
467.0929 641.3102 l
h
f*
469.3039 628.3276 m
478.8283 628.3276 l
h
f*
262.2614 576.3402 m
271.7858 576.3402 l
h
f*
477.5811 563.3008 m
487.1055 563.3008 l
h
f*
203.4142 550.3181 m
212.9386 550.3181 l
h
f*
274.6205 537.3354 m
284.0882 537.3354 l
h
f*
344.2394 498.3307 m
353.7638 498.3307 l
h
f*
358.2425 498.3307 m
367.7102 498.3307 l
h
f*
312.7748 485.348 m
322.2992 485.348 l
h
f*
326.778 485.348 m
336.2457 485.348 l
h
f*
467.263 472.3087 m
476.7874 472.3087 l
h
f*
418.4504 433.3039 m
427.9748 433.3039 l
h
f*
432.3969 433.3039 m
441.9213 433.3039 l
h
f*
491.6409 342.3118 m
496.4031 342.3118 l
h
f*
500.8252 342.3118 m
510.3496 342.3118 l
h
f*
514.8283 342.3118 m
524.3528 342.3118 l
h
f*
494.3055 329.3291 m
503.8299 329.3291 l
h
f*
508.3087 329.3291 m
517.7764 329.3291 l
h
f*
537.4488 316.3465 m
546.9165 316.3465 l
h
f*
544.6488 303.3071 m
554.1732 303.3071 l
h
f*
0 g
1 j
1 J
0 w
10 0 0 10 200.0125 707.4141 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(difficulty)Tj
3.8097 0 Td
(of)Tj
1.0148 0 Td
(obtaining)Tj
4.0592 0 Td
(structural)Tj
4.0818 0 Td
(properties)Tj
4.2747 0 Td
(even)Tj
2.0692 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(concentrated)Tj
5.4482 0 Td
(phase)Tj
2.4831 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(],)Tj
1.6044 0 Td
(and)Tj
1.7292 0 Td
(the)Tj
1.4683 0 Td
(cum-)Tj
-34.5484 -1.3039 Td
(bersome)Tj
3.6339 0 Td
(process)Tj
3.1805 0 Td
(of)Tj
1.0148 0 Td
(screening)Tj
4.0535 0 Td
(mutations)Tj
4.2803 0 Td
([)Tj
0.83 0.64 0.02 0 k
(35)Tj
0 g
(].)Tj
-14.9668 -1.2982 Td
(A)Tj
0.9014 0 Td
(number)Tj
3.4129 0 Td
(of)Tj
1.0091 0 Td
(recent)Tj
2.7042 0 Td
(theoretical)Tj
4.4334 0 Td
(and)Tj
1.7234 0 Td
(simulation)Tj
4.4901 0 Td
(studies)Tj
2.982 0 Td
(have)Tj
2.0523 0 Td
(addressed)Tj
4.1726 0 Td
(protein)Tj
3.1464 0 Td
(phase)Tj
2.4775 0 Td
(separa-)Tj
-34.7015 -1.2983 Td
(tion.)Tj
2.0636 0 Td
(Jacobs)Tj
2.7836 0 Td
(and)Tj
1.7291 0 Td
(Frenkel)Tj
3.2598 0 Td
(used)Tj
2.0579 0 Td
(Monte)Tj
2.8914 0 Td
(Carlo)Tj
2.4434 0 Td
(simulations)Tj
4.8529 0 Td
(to)Tj
1.0261 0 Td
(study)Tj
2.3925 0 Td
(multiple-component)Tj
8.5095 0 Td
(phase)Tj
-34.0098 -1.2983 Td
(separation)Tj
4.3823 0 Td
(and)Tj
1.7291 0 Td
(found)Tj
2.6192 0 Td
(that)Tj
1.7801 0 Td
(the)Tj
1.4684 0 Td
(phase)Tj
2.4831 0 Td
(boundary)Tj
4.0989 0 Td
(is)Tj
0.8447 0 Td
(very)Tj
1.9276 0 Td
(sensitive)Tj
3.6226 0 Td
(to)Tj
1.0261 0 Td
(intermolecular)Tj
6.1285 0 Td
(interactions,)Tj
-32.1106 -1.3039 Td
(but)Tj
1.5533 0 Td
(less)Tj
1.6101 0 Td
(dependent)Tj
4.456 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.474 0 Td
(number)Tj
3.4186 0 Td
(of)Tj
1.0148 0 Td
(components)Tj
5.1703 0 Td
(in)Tj
1.0375 0 Td
(the)Tj
1.4683 0 Td
(system)Tj
2.9367 0 Td
([)Tj
0.83 0.64 0.02 0 k
(36)Tj
0 g
(].)Tj
2.0806 0 Td
(Lin)Tj
1.5704 0 Td
(and)Tj
1.7348 0 Td
(Chan)Tj
2.3924 0 Td
(applied)Tj
-33.1934 -1.2982 Td
(the)Tj
1.4683 0 Td
(random)Tj
3.4299 0 Td
(phase)Tj
2.4831 0 Td
(approximation)Tj
6.1738 0 Td
(to)Tj
1.0262 0 Td
(treat)Tj
2.0409 0 Td
(electrostatic)Tj
5.0003 0 Td
(interactions)Tj
4.9663 0 Td
([)Tj
0.83 0.64 0.02 0 k
(37)Tj
0 g
(])Tj
1.8481 0 Td
(and)Tj
1.7348 0 Td
(Flory-Huggins)Tj
-30.1717 -1.2983 Td
(theory)Tj
2.7949 0 Td
(for)Tj
1.3776 0 Td
(mixing)Tj
3.0501 0 Td
(entropy)Tj
3.3335 0 Td
(and)Tj
1.7235 0 Td
(other)Tj
2.3414 0 Td
(interactions.)Tj
5.1873 0 Td
(They)Tj
2.228 0 Td
(were)Tj
2.1147 0 Td
(able)Tj
1.8255 0 Td
(to)Tj
1.0204 0 Td
(capture)Tj
3.2088 0 Td
(the)Tj
1.4627 0 Td
(sequence)Tj
3.8494 0 Td
(spec-)Tj
-35.5178 -1.3039 Td
(ificity)Tj
2.4831 0 Td
(of)Tj
1.0148 0 Td
(charged)Tj
3.3959 0 Td
(amino)Tj
2.7949 0 Td
(acids)Tj
2.2337 0 Td
(and)Tj
1.7291 0 Td
(found)Tj
2.6192 0 Td
(that)Tj
1.7802 0 Td
(the)Tj
1.4683 0 Td
(dependence)Tj
5.0059 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(phase)Tj
2.4888 0 Td
(boundary)Tj
4.0932 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
-34.6051 -1.2983 Td
(IDP)Tj
1.8538 0 Td
(Ddx4)Tj
2.4264 0 Td
(on)Tj
1.2756 0 Td
(salt)Tj
1.5591 0 Td
(concentration)Tj
5.8166 0 Td
(can)Tj
1.6271 0 Td
(be)Tj
1.1509 0 Td
(explained)Tj
4.0705 0 Td
(by)Tj
1.1849 0 Td
(considering)Tj
4.9322 0 Td
(only)Tj
1.9729 0 Td
(electrostatic)Tj
4.9946 0 Td
(screening)Tj
-32.8646 -1.2983 Td
(in)Tj
1.0318 0 Td
(their)Tj
2.1089 0 Td
(model)Tj
2.7439 0 Td
([)Tj
0.83 0.64 0.02 0 k
(38)Tj
0 g
(].)Tj
2.0807 0 Td
(It)Tj
0.856 0 Td
(was)Tj
1.7008 0 Td
(also)Tj
1.7688 0 Td
(found)Tj
2.6192 0 Td
(that)Tj
1.7745 0 Td
(the)Tj
1.4683 0 Td
(monomer)Tj
4.2179 0 Td
(radius)Tj
2.7099 0 Td
(of)Tj
1.0148 0 Td
(gyration)Tj
3.566 0 Td
(\()Tj
/F11 1 Tf
[()]TJ
ET
Q
q
1 j
1 J
0 w
7.4999 0 0 6.6659 505.9275 575.7165 cm
BT
/F11 1 Tf
1 TL
-0.0053 Tc
0 0 Td
[()]TJ
ET
Q
q
1 j
1 J
0 w
10 0 0 10 509.0456 577.4173 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(\))Tj
0.5555 0 Td
(is)Tj
0.8504 0 Td
(correlated)Tj
-32.309 -1.3039 Td
(with)Tj
1.9956 0 Td
(the)Tj
1.4684 0 Td
(corresponding)Tj
6.0604 0 Td
(critical)Tj
2.9537 0 Td
(temperature)Tj
5.125 0 Td
(in)Tj
1.0375 0 Td
(both)Tj
2.0579 0 Td
(theoretical)Tj
4.4447 0 Td
(work)Tj
2.2734 0 Td
([)Tj
0.83 0.64 0.02 0 k
(39)Tj
0 g
(])Tj
1.8538 0 Td
(and)Tj
1.729 0 Td
(experiment)Tj
-30.9994 -1.2982 Td
([)Tj
0.83 0.64 0.02 0 k
(14)Tj
0 g
(].)Tj
2.075 0 Td
(This)Tj
1.9899 0 Td
(supports)Tj
3.6793 0 Td
(the)Tj
1.4684 0 Td
(hypothesis)Tj
4.4674 0 Td
(that)Tj
1.7744 0 Td
(fundamental)Tj
5.3178 0 Td
(polymer)Tj
3.5603 0 Td
(physics)Tj
3.1351 0 Td
(principles)Tj
4.1611 0 Td
(can)Tj
1.6271 0 Td
(be)Tj
1.1508 0 Td
(used)Tj
2.058 0 Td
(to)Tj
-36.4646 -1.2983 Td
(understand)Tj
4.7849 0 Td
(LLPS)Tj
2.3357 0 Td
([)Tj
0.83 0.64 0.02 0 k
(40)Tj
0 g
(].)Tj
2.075 0 Td
(However,)Tj
4.0762 0 Td
(a)Tj
0.6519 0 Td
(computational)Tj
6.0491 0 Td
(framework)Tj
4.6148 0 Td
(capable)Tj
3.2088 0 Td
(of)Tj
1.0148 0 Td
(capturing)Tj
4.0704 0 Td
(the)Tj
1.4684 0 Td
(general)Tj
-34.35 -1.3039 Td
(sequence)Tj
3.8551 0 Td
(specificity)Tj
4.2123 0 Td
(including)Tj
4.0422 0 Td
(both)Tj
2.0579 0 Td
(hydrophobic)Tj
5.3575 0 Td
(and)Tj
1.7347 0 Td
(electrostatic)Tj
4.9947 0 Td
(interactions)Tj
4.9661 0 Td
(and)Tj
1.7292 0 Td
(molecular)Tj
-32.9497 -1.2983 Td
(details)Tj
2.778 0 Td
(on)Tj
1.2756 0 Td
(both)Tj
2.0579 0 Td
(intra-)Tj
2.4888 0 Td
(and)Tj
1.7291 0 Td
(inter-molecular)Tj
6.48 0 Td
(interactions)Tj
4.9719 0 Td
(is)Tj
0.8447 0 Td
(still)Tj
1.6385 0 Td
(missing.)Tj
3.5376 0 Td
(All-atom)Tj
3.8039 0 Td
(simulation)Tj
4.4958 0 Td
(has)Tj
-36.1018 -1.2982 Td
(the)Tj
1.4684 0 Td
(potential)Tj
3.7587 0 Td
(of)Tj
1.0148 0 Td
(fulfilling)Tj
3.6113 0 Td
(both)Tj
2.0579 0 Td
(tasks)Tj
2.1714 0 Td
([)Tj
0.83 0.64 0.02 0 k
(41)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7404 0 Td
(42)Tj
0 g
(])Tj
1.5081 0 Td
(with)Tj
2.0012 0 Td
(the)Tj
1.4683 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(force)Tj
2.2337 0 Td
(fields)Tj
2.3358 0 Td
(suitable)Tj
3.2824 0 Td
(for)Tj
1.3832 0 Td
(intrinsically)Tj
-32.5811 -1.2983 Td
(disordered)Tj
4.5241 0 Td
(proteins)Tj
3.5149 0 Td
(\(IDPs\))Tj
2.897 0 Td
([)Tj
0.83 0.64 0.02 0 k
(43)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7405 0 Td
(44)Tj
0 g
(].)Tj
1.7348 0 Td
(Such)Tj
2.1713 0 Td
(a)Tj
0.6576 0 Td
(force)Tj
2.2337 0 Td
(field)Tj
1.9729 0 Td
(has)Tj
1.5421 0 Td
(been)Tj
2.1203 0 Td
(recently)Tj
3.4129 0 Td
(applied)Tj
3.152 0 Td
(to)Tj
1.0261 0 Td
(study)Tj
2.3868 0 Td
(the)Tj
-35.087 -1.3039 Td
(monomer)Tj
4.218 0 Td
(properties)Tj
4.2746 0 Td
(of)Tj
1.0148 0 Td
(TDP-43)Tj
3.4299 0 Td
(which)Tj
2.6475 0 Td
(is)Tj
0.8504 0 Td
(known)Tj
3.0047 0 Td
(to)Tj
1.0262 0 Td
(undergo)Tj
3.5886 0 Td
(LLPS)Tj
2.3301 0 Td
([)Tj
0.83 0.64 0.02 0 k
(45)Tj
0 g
(].)Tj
2.0806 0 Td
(However,)Tj
4.0761 0 Td
(computa-)Tj
-32.5415 -1.2983 Td
(tional)Tj
2.5172 0 Td
(efficiency)Tj
4.0308 0 Td
(imposes)Tj
3.4753 0 Td
(limits)Tj
2.4774 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.474 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(all-atom)Tj
3.5547 0 Td
(representation)Tj
6.015 0 Td
(for)Tj
1.3833 0 Td
(simulating)Tj
4.456 0 Td
(LLPS)Tj
-33.2048 -1.2983 Td
(directly.)Tj
3.4583 0 Td
(Even)Tj
2.2167 0 Td
(the)Tj
1.4683 0 Td
(use)Tj
1.5307 0 Td
(of)Tj
1.0148 0 Td
(coarse-grained)Tj
6.1285 0 Td
(simulations)Tj
4.8585 0 Td
(requires)Tj
3.4696 0 Td
(well-designed)Tj
5.7146 0 Td
(sampling)Tj
3.8833 0 Td
(methods)Tj
-33.7433 -1.3039 Td
(to)Tj
1.0262 0 Td
(overcome)Tj
4.1499 0 Td
(the)Tj
1.4683 0 Td
(enthalpy)Tj
3.668 0 Td
(gap)Tj
1.6384 0 Td
(between)Tj
3.5263 0 Td
(the)Tj
1.474 0 Td
(two)Tj
1.7065 0 Td
(phases)Tj
2.8459 0 Td
([)Tj
0.83 0.64 0.02 0 k
(46)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7348 0 Td
(47)Tj
0 g
(].)Tj
-22.042 -1.2982 Td
(In)Tj
1.1111 0 Td
(this)Tj
1.6725 0 Td
(work,)Tj
2.5058 0 Td
(we)Tj
1.3266 0 Td
(introduce)Tj
4.1159 0 Td
(a)Tj
0.6519 0 Td
(general)Tj
3.1351 0 Td
(computational)Tj
6.0491 0 Td
(framework)Tj
4.6148 0 Td
(for)Tj
1.3833 0 Td
(studying)Tj
3.6736 0 Td
(LLPS,)Tj
2.5568 0 Td
(combin-)Tj
-33.9928 -1.2983 Td
(ing)Tj
1.5024 0 Td
(a)Tj
0.652 0 Td
(residue)Tj
3.1237 0 Td
(based)Tj
2.4718 0 Td
(potential)Tj
3.7587 0 Td
(capable)Tj
3.2032 0 Td
(of)Tj
1.0148 0 Td
(capturing)Tj
4.0761 0 Td
(the)Tj
1.4684 0 Td
(sequence)Tj
3.8607 0 Td
(specific)Tj
3.1862 0 Td
(interactions)Tj
4.9718 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
-35.0189 -1.3039 Td
(slab)Tj
1.7688 0 Td
(simulation)Tj
4.4958 0 Td
(method)Tj
3.3221 0 Td
(capable)Tj
3.2032 0 Td
(of)Tj
1.0148 0 Td
(achieving)Tj
4.0365 0 Td
(convergence)Tj
5.2327 0 Td
(for)Tj
1.3833 0 Td
(phase)Tj
2.4831 0 Td
(transition)Tj
4.1215 0 Td
(properties)Tj
-31.0618 -1.2983 Td
(including)Tj
4.0422 0 Td
(critical)Tj
2.948 0 Td
(temperature,)Tj
5.3575 0 Td
(and)Tj
1.7291 0 Td
(protein)Tj
3.1521 0 Td
(concentration)Tj
5.8167 0 Td
(in)Tj
1.0374 0 Td
(dilute)Tj
2.5115 0 Td
(and)Tj
1.7291 0 Td
(concentrated)Tj
5.4481 0 Td
(phases.)Tj
-33.7717 -1.2982 Td
(To)Tj
1.338 0 Td
(demonstrate)Tj
5.2327 0 Td
(the)Tj
1.4683 0 Td
(capabilities)Tj
4.6658 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(model,)Tj
2.9707 0 Td
(we)Tj
1.3266 0 Td
(have)Tj
2.0636 0 Td
(selected)Tj
3.3448 0 Td
(two)Tj
1.7122 0 Td
(model)Tj
2.7439 0 Td
(proteins:)Tj
3.7359 0 Td
(the)Tj
1.4684 0 Td
(LC)Tj
-34.5541 -1.2983 Td
(domain)Tj
3.3222 0 Td
(of)Tj
1.0148 0 Td
(RNA-binding)Tj
5.743 0 Td
(protein,)Tj
3.3789 0 Td
(Fused)Tj
2.5908 0 Td
(in)Tj
1.0318 0 Td
(Sarcoma)Tj
3.685 0 Td
(\(FUS\),)Tj
2.8687 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4683 0 Td
(DEAD-box)Tj
4.7734 0 Td
(helicase)Tj
3.3279 0 Td
(pro-)Tj
-34.9339 -1.3039 Td
(tein,)Tj
1.9843 0 Td
(LAF-1,)Tj
3.0217 0 Td
(both)Tj
2.0579 0 Td
(of)Tj
1.0148 0 Td
(which)Tj
2.6476 0 Td
(are)Tj
1.4513 0 Td
(able)Tj
1.8312 0 Td
(to)Tj
1.0261 0 Td
(phase)Tj
2.4831 0 Td
(separate)Tj
3.481 0 Td
(in)Tj
1.0374 0 Td
(vitro)Tj
2.1147 0 Td
(and)Tj
1.7348 0 Td
(in)Tj
1.0318 0 Td
(vivo)Tj
1.9048 0 Td
([)Tj
0.83 0.64 0.02 0 k
(6)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.2586 0 Td
(15)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.4002 0 Td
(25)Tj
0 g
(].)Tj
1.7348 0 Td
(Mutations)Tj
-33.2161 -1.2983 Td
(of)Tj
1.0148 0 Td
(FUS)Tj
1.9559 0 Td
(have)Tj
2.0636 0 Td
(been)Tj
2.1203 0 Td
(shown)Tj
2.8517 0 Td
(to)Tj
1.0204 0 Td
(be)Tj
1.1509 0 Td
(highly)Tj
2.7099 0 Td
(relevant)Tj
3.4186 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.474 0 Td
(pathogenesis)Tj
5.3518 0 Td
(of)Tj
1.0148 0 Td
(ALS)Tj
1.9162 0 Td
([)Tj
0.83 0.64 0.02 0 k
(48)Tj
0 g
(,)Tj
0.83 0.64 0.02 0 k
1.7404 0 Td
(49)Tj
0 g
(])Tj
1.508 0 Td
(and)Tj
1.7291 0 Td
(display)Tj
-34.0665 -1.2983 Td
(the)Tj
1.4684 0 Td
(ability)Tj
2.6929 0 Td
(to)Tj
1.0261 0 Td
(alter)Tj
1.9956 0 Td
(the)Tj
1.4683 0 Td
(kinetics)Tj
3.3052 0 Td
(of)Tj
1.0148 0 Td
(both)Tj
2.0579 0 Td
(droplet)Tj
3.1125 0 Td
(formation)Tj
4.2632 0 Td
(and)Tj
1.7292 0 Td
(aggregation)Tj
4.8982 0 Td
(into)Tj
1.8425 0 Td
(fibrils)Tj
2.5284 0 Td
([)Tj
0.83 0.64 0.02 0 k
(15)Tj
0 g
(].)Tj
2.0749 0 Td
(In)Tj
-35.4781 -1.3039 Td
(addition,)Tj
3.8211 0 Td
(both)Tj
2.058 0 Td
(the)Tj
1.474 0 Td
(full)Tj
1.525 0 Td
(length)Tj
2.7326 0 Td
(and)Tj
1.7291 0 Td
(disordered)Tj
4.5297 0 Td
(domain)Tj
3.3222 0 Td
(of)Tj
1.0148 0 Td
(LAF-1)Tj
2.795 0 Td
(phase)Tj
2.4831 0 Td
(separate)Tj
3.4808 0 Td
(in)Tj
1.0375 0 Td
(vitro)Tj
2.1203 0 Td
([)Tj
0.83 0.64 0.02 0 k
(25)Tj
0 g
(],)Tj
-34.1232 -1.2982 Td
(allowing)Tj
3.617 0 Td
(us)Tj
1.1112 0 Td
(to)Tj
1.0205 0 Td
(explore)Tj
3.1747 0 Td
(the)Tj
1.4741 0 Td
(impact)Tj
2.9763 0 Td
(of)Tj
1.0148 0 Td
(a)Tj
0.652 0 Td
(large,)Tj
2.3867 0 Td
(rigid)Tj
2.1203 0 Td
(domain)Tj
3.3222 0 Td
(on)Tj
1.2756 0 Td
(the)Tj
1.4683 0 Td
(LLPS)Tj
2.3358 0 Td
(behavior.)Tj
-26.7532 -1.2983 Td
(The)Tj
1.7858 0 Td
(manuscript)Tj
4.7848 0 Td
(is)Tj
0.8504 0 Td
(organized)Tj
4.1782 0 Td
(as)Tj
1.0148 0 Td
(follows.)Tj
3.2825 0 Td
(First,)Tj
2.2734 0 Td
(we)Tj
1.3266 0 Td
(introduce)Tj
4.1159 0 Td
(our)Tj
1.6271 0 Td
(computational)Tj
6.049 0 Td
(framework)Tj
-32.4848 -1.3039 Td
(including)Tj
4.0422 0 Td
(the)Tj
1.4684 0 Td
(coarse-grained)Tj
6.1284 0 Td
(potential,)Tj
3.9855 0 Td
(the)Tj
1.4683 0 Td
(sampling)Tj
3.8778 0 Td
(method)Tj
3.3279 0 Td
(and)Tj
1.7291 0 Td
(the)Tj
1.4683 0 Td
(treatment)Tj
4.1385 0 Td
(of)Tj
1.0148 0 Td
(folded)Tj
2.7382 0 Td
(pro-)Tj
-35.3874 -1.2983 Td
(teins)Tj
2.1147 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(simulations.)Tj
5.0853 0 Td
(We)Tj
1.6101 0 Td
(then)Tj
2.0182 0 Td
(present)Tj
3.1635 0 Td
(the)Tj
1.4683 0 Td
(application)Tj
4.6828 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4683 0 Td
(method)Tj
3.3222 0 Td
(using)Tj
2.3925 0 Td
(two)Tj
1.7063 0 Td
(model)Tj
2.7439 0 Td
(sys-)Tj
-35.2967 -1.2983 Td
(tems.)Tj
2.3471 0 Td
(For)Tj
1.6271 0 Td
(the)Tj
1.4683 0 Td
(first)Tj
1.8028 0 Td
(system,)Tj
3.1635 0 Td
(we)Tj
1.3323 0 Td
(show)Tj
2.296 0 Td
(the)Tj
1.474 0 Td
(comparison)Tj
4.972 0 Td
(of)Tj
1.0148 0 Td
(phase)Tj
2.4831 0 Td
(diagrams)Tj
3.9004 0 Td
(for)Tj
1.389 0 Td
(wild-type)Tj
3.9854 0 Td
(\(WT\))Tj
2.4775 0 Td
(FUS)Tj
-35.7333 -1.3039 Td
(and)Tj
1.7292 0 Td
(a)Tj
0.6519 0 Td
(set)Tj
1.304 0 Td
(of)Tj
1.0148 0 Td
(mutants,)Tj
3.736 0 Td
(and)Tj
1.7291 0 Td
(that)Tj
1.7802 0 Td
(they)Tj
1.9218 0 Td
(are)Tj
1.4457 0 Td
(qualitatively)Tj
5.0797 0 Td
(consistent)Tj
4.2576 0 Td
(with)Tj
2.0012 0 Td
(recent)Tj
2.7042 0 Td
(experimental)Tj
5.4594 0 Td
(mea-)Tj
-34.8148 -1.2982 Td
(surements.)Tj
4.5808 0 Td
(For)Tj
1.6214 0 Td
(the)Tj
1.474 0 Td
(second,)Tj
3.2372 0 Td
(we)Tj
1.3266 0 Td
(demonstrate)Tj
5.2327 0 Td
(how)Tj
1.9389 0 Td
(inclusion)Tj
3.9174 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(folded)Tj
2.7382 0 Td
(domain)Tj
3.3221 0 Td
(alters)Tj
2.3584 0 Td
(the)Tj
-34.2309 -1.2983 Td
(LAF-1)Tj
2.795 0 Td
(phase)Tj
2.4831 0 Td
(diagram.)Tj
3.7644 0 Td
(In)Tj
1.1112 0 Td
(both)Tj
2.0579 0 Td
(FUS)Tj
1.9616 0 Td
(and)Tj
1.7291 0 Td
(LAF-1,)Tj
3.0217 0 Td
(we)Tj
1.3266 0 Td
(show)Tj
2.3017 0 Td
(the)Tj
1.4684 0 Td
(flexibility)Tj
3.9514 0 Td
(of)Tj
1.0148 0 Td
(the)Tj
1.4684 0 Td
(framework)Tj
4.6147 0 Td
(by)Tj
-35.07 -1.2983 Td
(providing)Tj
4.1443 0 Td
(the)Tj
1.4683 0 Td
(results)Tj
2.812 0 Td
(for)Tj
1.3832 0 Td
(two)Tj
1.7122 0 Td
(different)Tj
3.6566 0 Td
(coarse-grained)Tj
6.1285 0 Td
(potentials.)Tj
4.3427 0 Td
(Lastly,)Tj
2.7779 0 Td
(we)Tj
1.3323 0 Td
(investigate)Tj
4.4559 0 Td
(the)Tj
-34.2139 -1.3039 Td
(phase)Tj
2.4832 0 Td
(diagram)Tj
3.5376 0 Td
(dependence)Tj
5.0059 0 Td
(on)Tj
1.2756 0 Td
(chain)Tj
2.4208 0 Td
(length,)Tj
2.9593 0 Td
(closely)Tj
2.88 0 Td
(related)Tj
2.9424 0 Td
(to)Tj
1.0261 0 Td
(the)Tj
1.4683 0 Td
(multivalency)Tj
6.1511 0 Td
(effect)Tj
2.3641 0 Td
(often)Tj
-34.5144 -1.2982 Td
(discussed)Tj
3.9969 0 Td
(in)Tj
1.0374 0 Td
(the)Tj
1.4684 0 Td
(context)Tj
3.1861 0 Td
(of)Tj
1.0148 0 Td
(LLPS.)Tj
ET
Q
q
1 j
1 J
0 w
11.9999 0 0 11.9999 200.0125 131.0173 cm
BT
/F2 1 Tf
1 TL
-0.0033 Tc
0 0 Td
(Methods)Tj
/F12 1 Tf
0 -1.5023 Td
(Coarse-grained)Tj
6.6142 0 Td
(model)Tj
2.8346 0 Td
(development)Tj
ET
Q
q
1 j
1 J
0 w
10 0 0 10 200.0125 95.9811 cm
BT
/F8 1 Tf
1 TL
-0.004 Tc
0 0 Td
(All-atom)Tj
3.804 0 Td
(simulations)Tj
4.8586 0 Td
(are)Tj
1.4456 0 Td
(unable)Tj
2.9084 0 Td
(to)Tj
1.0261 0 Td
(reach)Tj
2.3981 0 Td
(the)Tj
1.474 0 Td
(time)Tj
2.0239 0 Td
(scales)Tj
2.4718 0 Td
(needed)Tj
3.0954 0 Td
(to)Tj
1.0262 0 Td
(study)Tj
2.3867 0 Td
(phase)Tj
2.4832 0 Td
(separation)Tj
4.3823 0 Td
(with)Tj
-35.7843 -1.2982 Td
(current)Tj
3.1804 0 Td
(state-of-the-art)Tj
6.2362 0 Td
(computational)Tj
6.0491 0 Td
(hardware)Tj
3.9968 0 Td
(resources)Tj
3.9855 0 Td
(and)Tj
1.7348 0 Td
(sampling)Tj
3.8778 0 Td
(methods.)Tj
3.9061 0 Td
(We)Tj
ET
Q
q
1 j
1 J
0 w
576 737.1 m
36 737.1 l
36 737.6 l
576 737.6 l
f*
36 741.2598 169.285 23.6976 re
W* n
q
169.2283 0 0 23.6409 36 741.3165 cm
q
/I0 Do
Q
Q
Q
q
0 0 612 792 re
W* n
1 j
1 J
0 w
7.9999 0 0 7.9999 356.9385 745.7952 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(Sequenc)Tj
3.8764 0 Td
(e)Tj
0.7653 0 Td
(determinants)Tj
5.9032 0 Td
(of)Tj
1.0418 0 Td
(protein)Tj
3.2173 0 Td
(liquid-liqu)Tj
4.1174 0 Td
(id)Tj
0.9779 0 Td
(phase)Tj
2.8985 0 Td
(separati)Tj
3.4866 0 Td
(on)Tj
ET
Q
q
1 j
1 J
0 w
36 48.0002 m
576 48.0002 l
576 47.5002 l
36 47.5002 l
f*
0.83 0.64 0.02 0 k
142.5827 34.9228 m
295.8236 34.9228 l
h
f*
0 g
7.9999 0 0 7.9999 36 36 cm
BT
/F0 1 Tf
1 TL
-0.005 Tc
0 0 Td
(PLOS)Tj
2.8559 0 Td
(Computationa)Tj
6.1229 0 Td
(l)Tj
0.4322 0 Td
(Biology)Tj
3.4371 0 Td
(|)Tj
0.83 0.64 0.02 0 k
0.4748 0 Td
(https:/)Tj
2.6788 0 Td
(/doi.org/10.13)Tj
6.0094 0 Td
(71/journal.p)Tj
5.1166 0 Td
(cbi.1005941)Tj
0 g
6.3497 0 Td
(January)Tj
3.7134 0 Td
(24,)Tj
1.5874 0 Td
(2018)Tj
26.3624 0 Td
(3)Tj
0.7654 0 Td
(/)Tj
ET
endstream
endobj
135 0 obj
<>stream
endstream
endobj
136 0 obj
<>stream
endstream
endobj
137 0 obj
<>stream
endstream
endobj
138 0 obj
<>stream
endstream
endobj
139 0 obj
<>stream
endstream
endobj
140 0 obj
<>stream
endstream
endobj
141 0 obj
<>stream
endstream
endobj
142 0 obj
<>stream
endstream
endobj
143 0 obj
<>stream
endstream
endobj
144 0 obj
<>stream
endstream
endobj
145 0 obj
<>stream
endstream
endobj
146 0 obj
<>stream
endstream
endobj
147 0 obj
<>stream
endstream
endobj
148 0 obj
<>stream
endstream
endobj
149 0 obj
<>stream
endstream
endobj
150 0 obj
<>stream
endstream
endobj
151 0 obj
<>stream
endstream
endobj
152 0 obj
<>stream
endstream
endobj
153 0 obj
<>stream
endstream
endobj
154 0 obj
<>stream
endstream
endobj
155 0 obj
<>stream
BT
66.402 0 Td
(23)Tj
ET
Q
endstream
endobj
156 0 obj
<>/XObject<>>>/CropBox[0 0 612 792]/MediaBox[0 0 612 792]/Parent 11 0 R/Annots 165 0 R/Contents 166 0 R/TrimBox[0 0 612 792]>>
endobj
164 0 obj
<>/ProcSet[/PDF/ImageC]/Properties<>/XObject<>>>/Filter/FlateDecode/Length 116>>stream
h$;0D=\ kcQDA(8 BXs=͛Q!MWg!
bƔڡ
ŏm} XͶd`F,ƙ1?0ERmD=:+ @
endstream
endobj
167 0 obj
<>
endobj
168 0 obj
<<>>
endobj
169 0 obj
<>stream
Adobe d
4
s !1AQa"q2B#R3b$r%C4Scs5D'6Tdt&
EFVU(eufv7GWgw8HXhx)9IYiy*:JZjz m !1AQa"q2#BRbr3$4CS%cs5DT
&6E'dtU7()euFVfvGWgw8HXhx9IYiy*:JZjz ? v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]#rGȟ:n{5vlZiLXUarW_zǖ}5˖R+YʲEѩ LGSqUO"4i^jݾN.nKpZoMXTWV/o{ TWMSŦy-HѬ+H2քb xm|:&uT`W)~<ˋS^w?Ox<OVhլ, EhfD@OEv⯻#eQ,L
A_v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثV(%k?l9I HhZ>bԕo5icÅy oaA>nFLsHD?,.?Ŧ#Yjv{'; ɟͷ+~dh]H"ۆ&
=XWǕ2ve1kϬXh ]Cx#$BPd2 E4JIAZ^(\6q8Wb]v*UثWb]v*UثWb_ ylyCKkc=o;Dװ jqkxrKrS^gklkH R@wEqW*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb ɾA'`<۟lUUsLQ x`FoD~b?էIxO.Ҵ4ZUOG+^Eʹ$hWWGCPA،U+&I .ߗV nI-(?* Qy 9?Jy Z634>Z̧%>oM`% * ~i?ɿߙQ WGg~gjZ/QDʄl#n4S1-_?A /4Jl5{t+ pREV^B5_F~P"oO#yko.4Lְ$EHVi㊽v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]~f_~} -$_!]h{-ՠ,eSK_[>4S@ڝ1WT SL.ZTlsS`:Ozl:Tb | 9_yrYNHoȴhͲ^hg~(݉)JX
9 oxr Z5
o D^*Ŏ*r/ Ŷ藷s4i IGZt Ug_MyP}@\Na
'
"(oJ_ab]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]H {3jqi$/+]bܙcDSѡ:_srd6,4vC7$py)QS}
9 ?ʿ[K .峹q!IZXÕ;&"5=W'iwWӢttqUeaPAQWb]v*UثWb]v*UثWb]v*UثWb]v*UثWb]h:[B={٣:ӔWvT-uk-EKN1:>t8(vjMÛa&|8pk4$