您的位置 首页 工具使用

计算机蛋白质设计的工具

发布: 2021-07-27 1,902阅读 228评论

近年来随着计算机运算能力的提升以及先进算法的涌现，计算机辅助蛋白设计逐渐成为蛋白质工程的研究热点。其中DBTL（design-build-test-learn）循环（图1）是计算机辅助蛋白设计在挖掘新功能酶或改造现有酶的主要思路。

以结构模拟与能量计算为基础的蛋白质计算设计不但能改造酶的底物特异性与热稳定性，还可从头设计具有特定功能的人工酶。在学习和设计模块中，一系列的计算方法，如易于操作的结构预测和分子对接、大规模分子动力学(MD)模拟、高精度量子力学(QM)计算、数据驱动的机器学习和用户友好的网络工具，极大地帮助蛋白质工程改进甚至定制各种功能。

图1 计算辅助加速蛋白质工程

目前应用于蛋白质工程的主要计算工具总结如表1所示。表1列出了目前较为常用的蛋白质结构预测工具、分子对接工具、蛋白质通道计算工具、配体通道工具、分子动力学模拟工具、量子力学与分子力学结合模拟工具、突变靶点确认工具以及可完成多目的Rosetta工具包。其中配体通道工具的是基于分子对接方法预测配体与蛋白之间结合与解结合过程的结构变化，目前应用于蛋白从头设计工程。Gaussian作为QM量化软件，同时支持AMBER等力场，以ONIOM方式计算QM/MM；ORCA同样作为QM量化软件则支持CHARMM力场。另外，QM/MM一项中的chemshell工具是一种接口。当QM量化软件和MM没有相应接口时，如DL-POLY和Gaussian不能同时使用，即想用Gaussian算QM，想用DL-POLY算MM无法实现同时对QM/MM进行计算，chemshell则作为平台出现，可以同时调用上述两个量化软件，支持QM/MM同时进行。

表 1 蛋白质工程的计算工具

Target property Tools Distribution URL
protein structure MODELLER SM https://salilab.org/modeller
I-TASSER WS http://zhanglab.ccmb.med.umich.edu/I-TASSER
trRosetta WS https://yanglab.nankai.edu.cn/trRosetta
molecular docking AutoDock SM http://autodock.scripps.edu
UCSF DOCK SL http://dock.compbio.ucsf.edu
rDock SL http://rdock.sourceforge.net
protein channel Caver Analyst SM http://www.caver.cz
CHEXVIS WS http://vgl.serc.iisc.ernet.in/chexvis
ligand transport CaverDock WS https://loschmidt.chemi.muni.cz/caverweb
MM GROMACS SL http://www.gromacs.org/
AMBER SL http://ambermd.org
NAMD SL http://www.ks.uiuc.edu/Research/namd
QM and MM Gaussian SM https://gaussian.com
ORCA SL https://orcaforum.kofo.mpg.de
QM/MM ChemShell SL https://orcaforum.kofo.mpg.de
protein design HotSpot Wizard SL https://loschmidt.chemi.muni.cz/hotspotwizard
multipurpose Rosetta SL http://www.rosettacommons.org
在蛋白质工程中，确定突变位点后，下一步就是评估该位点特定突变对蛋白质目标属性的影响。根据评估功能的类型对工具进行了分组，一共7个工具，这些工具可用于根据特定位点突变的效果预测，如表2所示：

表2 用于预测突变效果的工具

Target property Tools URL
protein–protein interactions MutaBind http://www.ncbi.nlm.nih.gov/projects/mutabind/
iSEE Be provided as an R-model
mCSM-PPI2 http://biosig.unimelb.edu.au/mmcsm_ppi
interactions of the protein with nucleic acids and ligands mCSM-NA http://structure.bioc.cam.ac.uk/mcsm na.
PremPDI https://lilab.jysw.suda.edu.cn/research/PremPDI/
mCSM-lig http://structure.bioc.cam.ac.uk/mcsm_lig
protein dynamics and stability DynaMut http://biosig.unimelb.edu.au/dynamut/
这工具的功能主要包括预测蛋白-蛋白相互作用、蛋白与核酸或其他配体的相互作用以及蛋白质动力学及稳定性。

2018年，全球蛋白质工程市场评估为19亿美元，预计2024年将达到39亿美元，同年复合增长率(CAGR)将达到12.4%。而目前针对蛋白质的智能化计算设计研究，国内外都仍处在起步阶段，是我国蛋白质设计领域比肩世界水平的机遇。因此，处理好人工智能在蛋白质设计改造领域的应用，开发蛋白质计算设计新技术，解决关键技术难题，是蛋白质计算设计今后发展的主要道路。

参考文献：

1.Computer- aidedunderstanding  and engineering of enzymatic selectivity. DOI: 10.1016/j.biotechadv.2021.107793. 2021.
2.CSM- NA: predictingthe effects of mutations on protein  nucleic acids interactions. DOI: 10.1093/nar/gkx236.2017.
3.mmCSM-  PPI: predictingthe effects of multiple point mutations on protein-  protein interactions. DOI: 10.1093/nar/gkab273.2021.
4.iSEE: Interfacestructure, evolution, and energy-  based machine learning predictor of bindingaffinity changes upon mutations. DOI: 10.1002/prot.25630. 2018.
5.MutaBind estimatesand interprets the effects of sequence variants on protein- protein interactions.10.1093/nar/gkw374. 2016.
951赞
标签:



相关文章

回复 Aerwxl 取消回复

您的电子邮箱地址不会被公开。 必填项已用*标注

评论列表(228)

  6. I think the admin of this site is actually working hard in support of his web page, for the reason that here every material is quality based data.

    回复

  14. Good blog you have got here.. It is difficult to find quality writing like yours nowadays. I honestly appreciate people like you! Take care!!

    [url=https://teamcreed.cloud/latest/india-msf-supports-survivors-sexual-violence-aftermath-coronavirus-lockdown]teamcreed.cloud[/url]

    回复

  18. Patients have been successfully treated with a total daily dosage of 6 12 grams divided into 2, 3 or 4 administrations ranging from 1 [url=https://fastpriligy.top/]buy generic priligy[/url] An example of this is the medicine naltrexone, which has a bioavailability of 5 40 in healthy individuals

    回复
  22. 📖 Ticket- + 1,823487542 BTC. Verify > https://telegra.ph/Go-to-your-personal-cabinet-08-25?hs=69b44f37163b718738f3ac8ef964fa1b& 📖说道：

    n8zkut

    回复

  45. “Maybe his dad is right.” He thinks to himself as he continues with his intense fondling of his fiery red cock.

    回复

  50. “Stoke your cock while you sniff that jock.” He lifts his head from its bowed stance and looks into the eyes of his father wanting some acknowledgement.

    回复

  52. Kudos! I enjoy it.
    new jersey new online casino [url=https://usagamblinghub.com/#]best online casinos for usa[/url] 1xbet free online casino

    回复

  53. Regards, Loads of tips.
    online real cash casino games [url=https://usacasinomaster.com/#]no deposit online casino usa[/url] 5 min deposit online casino

    回复

  54. His father unbuttons his shirt and throws it to the bathroom floor. Where his son is like the mythical David, cast in stone with blonde locks and cherubic face. The father is dark and with a day’s growth of stubble on his face. [url=https://arturzasada.pl/]polskie porno[/url] “What happened at today’s practice today that was so different from any other day, son?” His dad asks.

    回复

  55. Nicely put. Regards!
    are online casinos legal in oklahoma [url=https://luckyusaplay.com/#]online casinos usa[/url] colosseum casino online

    回复

  56. Helpful knowledge. Thanks!
    do online casinos report your winnings to the irs [url=https://luckyusaplay.com/#]united states online casino[/url] online casino script

    回复

  60. Thanks a lot, I value this.
    online casino in italy [url=https://uscasinoguides.com/#]online casino bonuses[/url] online casinos no deposit sign up bonus

    回复

  62. Great stuff. Regards.
    online casino industry news [url=https://usaplayerscasino.com/#]play online casino[/url] ballys pa online casino

    回复

  63. You suggested it superbly!
    online casino mit lastschrift einzahlung [url=https://usagamblinghub.com/#]online casino bonus[/url] sweepstakes casino games online

    回复

  65. With thanks, Valuable stuff.
    casino royale 007 online [url=https://usacasinomaster.com/#]online american casinos[/url] online flash casino games

    回复

  67. Cheers. An abundance of forum posts!
    big win casino online real money [url=https://luckyusaplay.com/#]casinos online[/url] best australian online casino payid

    回复

  71. Appreciate it. Numerous postings!
    casino online netherlands [url=https://usaplayerscasino.com/#]free casino online[/url] safest online casino for us players

    回复

  72. You’ve made your point very nicely.!
    how do i withdraw money from online casino [url=https://usagamblinghub.com/#]casino play online[/url] online no deposit casinos usa

    回复

  73. Thanks a lot! Good stuff!
    crear cuenta casino online [url=https://usacasinomaster.com/#]new usa online casinos[/url] woo online casino

    回复

  75. Amazing write ups. Many thanks.
    better bets online casino [url=https://luckyusaplay.com/#]best online casino mentor[/url] sky vegas online casino

    回复

  78. Good stuff. Many thanks!
    cool cat online casino instant play [url=https://uscasinoguides.com/#]casino online casino[/url] juwa 777 online casino

    回复

  80. You have made your stand pretty nicely.!
    baywatch online casino [url=https://usaplayerscasino.com/#]best casinos online[/url] casino online bonuses

    回复

  81. You expressed it really well!
    casino online snai [url=https://usagamblinghub.com/#]best usa online casino[/url] sweeps online casino

    回复

  83. Nicely put. Thanks.
    united states online casino no deposit bonus [url=https://usacasinomaster.com/#]online gambling casino[/url] free online games casino slots

    回复

  85. Incredible plenty of excellent knowledge.
    rivers casino online slots [url=https://luckyusaplay.com/#]online casino free play[/url] best online casino instant payout

    回复

  88. Well expressed truly! !
    jackpot city online casino downloadable content [url=https://uscasinoguides.com/#]best online casinos for usa[/url] new online casino 2016

    回复

  90. Superb content. Regards.
    treasure island online casino [url=https://usaplayerscasino.com/#]best online casinos for usa[/url] using credit card for online casino

    回复

  91. Fantastic info. With thanks.
    how to scam online casinos [url=https://usagamblinghub.com/#]online casino free play[/url] no deposit bonus usa online casinos

    回复

  93. Incredible plenty of wonderful facts!
    online casinos klarna [url=https://usacasinomaster.com/#]usa casino online[/url] online casino finland

    回复

  97. You revealed this exceptionally well.
    indiana online casino [url=https://uscasinoguides.com/#]new casino online[/url] casino war online game

    回复

  99. Kudos! Ample material!
    silver oak online casino [url=https://usaplayerscasino.com/#]online betting casino[/url] online casino app ios

    回复

  101. Very well expressed truly. .
    yamaava online casino [url=https://usagamblinghub.com/#]best online casinos that payout[/url] online casinos las vegas

    回复

  103. You actually said this superbly!
    777 casino online download [url=https://usacasinomaster.com/#]casino online games free[/url] online casino sign up bonus no deposit real money

    回复

  104. Thanks a lot! Very good stuff.
    newest pa online casino [url=https://luckyusaplay.com/#]no deposit bonus online casinos[/url] 747 online casino logo

    回复

  107. You actually expressed that fantastically.
    online betting casino games [url=https://usaplayerscasino.com/#]most trusted online casinos for usa players[/url] ri online casino bonus

    回复

  109. Nicely put, Many thanks!
    online casino that accepts mastercard [url=https://usagamblinghub.com/#]social casinos online[/url] mo online casino

    回复

  112. You actually suggested this very well!
    vegas casino online no deposit bonus 2022 [url=https://luckyusaplay.com/#]online casino top rated[/url] casinos online in italy

    回复

  114. Thanks a lot. Excellent stuff.
    online casino bonuses in sweden [url=https://uscasinoguides.com/#]casino games online free[/url] hard rock online casino florida real money

    回复

  115. Fantastic posts. Cheers.
    roulette online casino live indonesia [url=https://usaplayerscasino.com/#]free online casinos[/url] casino online ohio

    回复

  117. Regards, I like it!
    online casino fish [url=https://usagamblinghub.com/#]best casino online[/url] slots inferno online casino

    回复

  119. Regards. Plenty of material.
    crazy time casino online philippines [url=https://usacasinomaster.com/#]free play online casino[/url] best dutch online casino

    回复

  124. Really a good deal of valuable info!
    safe online casino real money [url=https://luckyusaplay.com/#]best online casino reddit no deposit bonus[/url] best zar online casino

    回复
联系我们

联系我们

(44)07934433023

在线咨询: QQ交谈

邮箱: info@bioengx.org

关注微信
微信扫一扫关注我们

微信扫一扫关注我们

关注微博
返回顶部