This lesson is only available in Korean for now.
Dr. Son's mRNA Vaccine Design, First Steps IV

The same protein
can be spelled many ways

Take the 309-amino-acid construct from part III and rewrite it in spelling a human cell reads easily. There are sixty-one codons for twenty amino acids, so there is freedom to choose - and how that freedom is spent fixes both translation efficiency and structural stability.
The spine of this part is one line: MFE scales with length. -1231.20 (3819 nt) and -299.50 (927 nt) cannot be compared as they stand; divide by length and they become -0.3224 and -0.3231, essentially identical. That one division is what this course is worth.
Python runs right inside this page. There is nothing to install.

๐Ÿ Python๐ŸŽผ codon optimisation๐Ÿ“ length normalisation ๐ŸงŠ secondary structureโš–๏ธ lambda = 3๐Ÿ”ฌ ViennaRNA๐Ÿ‡ฌ๐Ÿ‡ง English
Start lesson 1 โ†’

How you'll learn

๐Ÿ“Divide by length first

-1231.20 and -299.50 cannot be compared as they stand. Divided, they are -0.3224 and -0.3231 - essentially the same.

โš–๏ธFeel the two objectives pull

Translation efficiency and structural stability pull against each other. That tension lives in a single knob, lambda.

๐Ÿ–๏ธCount it yourself

A CAI needs only a small usage table. Lesson 4 does it in three steps.

๐ŸšงSeparate prediction from result

A good CAI is not measured expression. Lesson 20 tabulates what may and may not be claimed.

Full curriculum

01
๊ฐ™์€ ๊ณก์„ ๋‹ค๋ฅธ ์•…๋ณด๋กœ ์ ๋Š”๋‹ค โ€” ๊ทธ๋Ÿฐ๋ฐ ์•…๋ณด๊ฐ€ ์—ฐ์ฃผ๋ฅผ ๋ฐ”๊พผ๋‹ค
Step 4 ยท ์™œ ์ด ๊ฑธ์Œ์ด ์žˆ๋‚˜
โœ“
02
์ฝ”๋ˆ ํŽธํ–ฅ โ€” ์ƒ๋ฌผ๋งˆ๋‹ค ์ฆ๊ฒจ ์“ฐ๋Š” ์ฒ ์ž๊ฐ€ ์žˆ๋‹ค
Step 4 ยท ์ˆ™์ฃผ๋ฅผ ์‚ฌ๋žŒ์œผ๋กœ ๊ณ ๋ฅด๋Š” ๊นŒ๋‹ญ
โœ“
03
CAI โ€” 1.0 ์ด ๋œปํ•˜๋Š” ๊ฒƒ๊ณผ, ์•„๋ฌด๋„ ๊ฑฐ๊ธฐ ๊ฐ€์ง€ ์•Š๋Š” ๊นŒ๋‹ญ
Step 4 ยท ์ฝ”๋ˆ ์ ์‘ ์ง€์ˆ˜
โœ“
04
์†์œผ๋กœ ์„ธ์–ด ๋ณด๋Š” CAI โ€” ๋ง์ปค ๋„ค ๊ฐœ๋ฅผ ์ ์ˆ˜๋กœ ๋ฐ”๊พผ๋‹ค
Step 4 ยท ์‹ค์Šต ยท III ๊ถŒ์˜ EAAAK ยท GPGPG ยท AAY ยท KK
โœ“
05
๋จธ๋ฆฌํ•€๊ณผ ๊ณ ๋ฆฌ โ€” mRNA ๊ฐ€ ์Šค์Šค๋กœ ์ ‘ํ˜€ ๊ธธ์„ ๋ง‰๋Š”๋‹ค
Step 4 ยท RNA ์ด์ฐจ ๊ตฌ์กฐ
โœ“
06
MFE โ€” ๋‚ฎ์„์ˆ˜๋ก ์•ˆ์ •ํ•˜๋‹ค๋Š” ๋ง์˜ ๋œป
Step 4 ยท ์ตœ์†Œ ์ž์œ  ์—๋„ˆ์ง€ ยท kcal/mol
โœ“
07
MFE ๋Š” ๊ธธ์ด๋ฅผ ๋”ฐ๋ผ ์ปค์ง„๋‹ค โ€” ๊ทธ๋ž˜์„œ ๊ทธ๋Œ€๋กœ ๊ฒฌ์ค„ ์ˆ˜ ์—†๋‹ค
Step 4 ยท โˆ’1231.20 (3819 nt) ๋Œ€ โˆ’299.50 (927 nt)
โœ“
08
LinearDesign โ€” ๋‘ ๋ชฉํ‘œ๋ฅผ ํ•œ ์•Œ๊ณ ๋ฆฌ์ฆ˜์ด ํ•จ๊ป˜ ํ‘ผ๋‹ค
Step 4 ยท github.com/LinearDesignSoftware/LinearDesign ยท ๋ช…๋ น์ค„ํŒ
โœ“
09
ฮป ๋ผ๋Š” ์†์žก์ด โ€” ๊ตฌ์กฐ์™€ ์ฝ”๋ˆ ์‚ฌ์ด ์–ด๋””์— ์„ค ๊ฒƒ์ธ๊ฐ€
Step 4 ยท ฮป = 0 ยท 1~2 ยท 3 ยท 3 ์ดˆ๊ณผ ยท ๋…ผ๋ฌธ์€ 3
โœ“
10
๋…ผ๋ฌธ์ด ๋ฐ›์€ ๋‹ต โ€” CAI 0.81 ๊ณผ 0.83
Step 4 ยท ์ „์ฒด CDS ์™€ MEVC
โœ“
11
GC ํ•จ๋Ÿ‰ โ€” ๋„ˆ๋ฌด ๋†’์œผ๋ฉด ์™„๊ณ ํ•˜๊ณ  ๋„ˆ๋ฌด ๋‚ฎ์œผ๋ฉด ๋ฌด๋ฅด๋‹ค
Step 4 ยท 50.35% ยท 53.61% ยท ๊ถŒ์žฅ ๊ตฌ๊ฐ„ 30~70%
โœ“
12
๋Œ€์•ˆ ๋„๊ตฌ NovoPro โ€” ๊ทธ๋ฆฌ๊ณ  ํ”ผํ•ด์•ผ ํ•  ๋‘ ์ž๋ฆฌ
Step 4 ยท ExpOptimizer ยท Human ยท BamHI ยท XhoI
โœ“
13
๋น ์ง„ ๊ฐ’ โ€” NovoPro ๋Š” MFE ๋ฅผ ์ฃผ์ง€ ์•Š๋Š”๋‹ค
Step 4 ยท ๋„๊ตฌ ํ•˜๋‚˜๋กœ ๋๋‚˜์ง€ ์•Š๋Š”๋‹ค
โœ“
14
RNAfold ยท RNAeval ยท RNAplfold โ€” ์„ธ ๋ฌผ์Œ์— ์„ธ ๋„๊ตฌ
Step 4 ยท ViennaRNA
โœ“
15
์—ด๋ ค ์žˆ์–ด์•ผ ํ•˜๋Š” ์ž๋ฆฌ โ€” ๋…ผ๋ฌธ์ด CRITICAL STEP ์ด๋ผ ์ ์€ ๊ณณ
Step 4 ยท ์ ‘๊ทผ์„ฑ ยท ๋ฆฌ๋ณด์†œ ๊ฒฐํ•ฉ ์ž๋ฆฌ์™€ ์—ํ”ผํ† ํ”„ ๋‘˜๋ ˆ
โœ“
16
๊ทธ๋ฆผ ์ฝ๊ธฐ โ€” ์ƒ‰์€ ํ™•๋ฅ ์ด๊ณ , ๊ณก์„ ์€ ์…‹์ด๋‹ค
Step 4 ยท ์—ผ๊ธฐ์Œ ํ™•๋ฅ  0~1 ยท ๋งˆ์šดํ‹ด ํ”Œ๋กฏ
โœ“
17
๋‘ ํ•จ์ • โ€” ๊ธธ์ด๋ฅผ ๋ฌด์‹œํ•œ ๊ฒฌ์คŒ๊ณผ, ์˜ˆ์ธก์„ ๊ฒฐ๊ณผ๋กœ ์ฝ๊ธฐ
Step 4 ยท ๊ฐ€์žฅ ํ”ํ•œ ๋‘ ์‹ค์ˆ˜
โœ“
18
๋‹จ๋ฐฑ์งˆ ์ชฝ์—์„œ ํ•œ ๋ฒˆ ๋” โ€” PSIPRED ์™€ ๋„ํ‚นยท๋ถ„์ž๋™์—ญํ•™
Step 4 ยท ์„ ํƒ ๋‹จ๊ณ„ ยท ExPASy Translate โ†’ PSIPRED ยท ClusPro ยท PyMOL ยท GROMACS
โœ“
19
์ข…ํ•ฉ โ€” ๋‚ด ํ‘œ๋ฅผ ์ง์ ‘ ๋งŒ๋“ ๋‹ค, ๊ธธ์ด๋กœ ๋‚˜๋ˆˆ ์นธ๊นŒ์ง€
Step 4 ยท ์‹ค์Šต ์ข…ํ•ฉ ยท ๋…ผ๋ฌธ์˜ ํ‘œ๋ฅผ ๋‹ค์‹œ ๊ทธ๋ฆฐ๋‹ค
โœ“
20
Step 4 ๋’ค์— โ€” ๋งํ•  ์ˆ˜ ์žˆ๋Š” ๊ฒƒ๊ณผ ๋งํ•  ์ˆ˜ ์—†๋Š” ๊ฒƒ
Step 4 ยท ์ •๋ฆฌ ยท ๋ชจ๋“  ์ˆ˜์น˜๋Š” ์ธ์‹ค๋ฆฌ์ฝ” ์˜ˆ์ธก์ด๋‹ค
โœ“