溶剂可及性(一):基本概念

一、基本概念

​ 溶剂可及性(solvent accessibility)一般描述为可及表面积(access surface area,ASA)或者是 溶剂可及表面积(solvent-accessibility surface area,SASA),是溶剂可接触的生物分子表面积。 ASA的测量通常以平方埃为单位进行描述(分子生物学中的标准测量单位),通常使用“滚球算法”来计算ASA。

jjQ6sI.png

​ 简单来说,给定指定大小的小球在分子表面滚动,小球所经过的区域即是ASA,关于小球的具体大小,和ASA数学建模可以参考Gromiha和Ahmad,2005,Lee和Richards,1971,这里就不再进一步讨论(博主并非生物专业,没对ASA的生物意义进行进一步探究)。

​ 因此,倘若需要计算蛋白质中每个残基(氨基酸)的ASA,需要知道该蛋白质的三级结构,再利用滚球算法即可。计算ASA的算法有许多,ACCESS(1978), Naccess(1993), GETAREA(1998), DSSP(1983), ASC(1993), POPS(2003)。使用较多的是DSSP,后续文章中将介绍如何安装使用DSSP。

​ 至于为什么要研究溶剂可及性,主要概括为以下几点:

  • 研究蛋白折叠以及蛋白稳定性(可能是提高蛋白质二级和三级结构预测准确性的有效因素)
  • 计算蛋白和蛋白相互作用面的面积大小
  • 研究蛋白和配体结合自由能

​ 这三点的具体生物意义触及到博主的知识盲区,就不再过多解释。后文将给出一个具体的研究案例。

二、相对溶剂可及性

​ 对于一个已知结构的蛋白质,利用DSSP可以计算出每个残基的ASA。既然ASA与蛋白质的结构相关,那么相同的氨基酸(20种氨基酸)由于在蛋白质上所处位置的不同计算得到的ASA也会不同。因此,我们常用相对溶剂可及性(relative solvent accessibility,RSA)代替ASA来描述氨基酸。RSA的计算公式比较简单:
$$
RSA=\frac{ASA}{maxASA}
$$
$ASA$ 可以通过DSSP求得,$maxASA$ 则需要通过查表得到,下面是在维基百科查到的$maxASA$ 。

jjQyQA.png

可以看出,每一种氨基酸会对应一个$maxASA$ ,另外$maxASA$ 也随着研究不断更新,python的biopython库就含有$maxASA$ 的具体数值,在后续的文章中会简单介绍。

三、RSA与变异

Savojardo C, Manfredi M, Martelli P L, et al. Solvent accessibility of residues undergoing pathogenic variations in humans: from protein structures to protein sequences[J]. Frontiers in molecular biosciences, 2021, 7: 460.

蛋白质并不是一层不变的,在进化过程中会发生变异。简单来说变异分为有害变异(致病性变异)和无害变异(中性变异),经研究发现RSA的数值和变异的类型有着某种联系。该论文计算了已知单氨基酸变异(SRV)位点的RSA,根据RSA的值将所有残基划分为隐藏型(Buried)和暴露型(Exposed),划分的方法是统计每个残基的RSA,将RSA值最小的20%(threshold)认定为Buried,高于20%认定为Exposed,这里需要指出的是20%并不是指残基的20%,是统计所有残基的RSA值,选取所有RSA值中最小的20%对应的残基。20%并不是确定的threshold,也可以为其他数值。

当将所有残基分类后,统计发生变异位点的RSA的数值,得到以下结论:

jjQrzd.png

可以看出,致病性单氨基酸变异大多数发生在Buried位点,而中性变异大多发生在Exposed位点。因此,RSA背后确实有着一定的生物意义,或许还有更多的生物意义有待发现。

参考资料:

https://qinqianshan.com/bioinformatics/protein_design/solvent-accessibility/(蛋白溶剂可及性

https://www.bilibili.com/video/BV1ta4y1p7yR?spm_id_from=333.880.my_history.page.click(Pymol - 计算溶剂可及表面积(SASA))

https://en.wikipedia.org/wiki/Relative_accessible_surface_area(Relative accessible surface area)

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    You have customers waiting to talk with you right now… don’t keep them waiting.
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    If you’d like to unsubscribe click here http://jumboleadmagnet.com/unsubscribe.aspx?d=ayanokoujimonki.top

  20. Randy Chidley
    10月前
    2023-8-19 15:57:32

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  21. Eric Jones
    10月前
    2023-8-17 9:49:05

    Hello ayanokoujimonki.top Admin! Cool website!
    My name’s Eric, and I just found your site – ayanokoujimonki.top – while surfing the net. You showed up at the top of the search results, so I checked you out. Looks like what you’re doing is pretty cool.
    But if you don’t mind me asking – after someone like me stumbles across ayanokoujimonki.top, what usually happens?
    Is your site generating leads for your business?
    I’m guessing some, but I also bet you’d like more… studies show that 7 out 10 who land on a site wind up leaving without a trace.
    Not good.
    Here’s a thought – what if there was an easy way for every visitor to “raise their hand” to get a phone call from you INSTANTLY… the second they hit your site and said, “call me now.”
    You can –
    Web Visitors Into Leads is a software widget that’s works on your site, ready to capture any visitor’s Name, Email address and Phone Number. It lets you know IMMEDIATELY – so that you can talk to that lead while they’re literally looking over your site.
    CLICK HERE https://advanceleadgeneration.com to try out a Live Demo with Web Visitors Into Leads now to see exactly how it works.
    Time is money when it comes to connecting with leads – the difference between contacting someone within 5 minutes versus 30 minutes later can be huge – like 100 times better!
    That’s why we built out our new SMS Text With Lead feature… because once you’ve captured the visitor’s phone number, you can automatically start a text message (SMS) conversation.
    Think about the possibilities – even if you don’t close a deal then and there, you can follow up with text messages for new offers, content links, even just “how you doing?” notes to build a relationship.
    Wouldn’t that be cool?
    CLICK HERE https://advanceleadgeneration.com to discover what Web Visitors Into Leads can do for your business.
    You could be converting up to 100X more leads today!
    Eric
    PS: Web Visitors Into Leads offers a FREE 14 days trial – and it even includes International Long Distance Calling.
    You have customers waiting to talk with you right now… don’t keep them waiting.
    CLICK HERE https://advanceleadgeneration.com to try Web Visitors Into Leads now.
    If you’d like to unsubscribe click here http://advanceleadgeneration.com/unsubscribe.aspx?d=ayanokoujimonki.top

  22. Eric Jones
    10月前
    2023-8-16 13:15:30

    To the ayanokoujimonki.top Webmaster.
    My name’s Eric and for just a second, imagine this…

    • Someone does a search and winds up at ayanokoujimonki.top.
    • They hang out for a minute to check it out. “I’m interested… but… maybe…”
    • And then they hit the back button and check out the other search results instead.
    • Bottom line – you got an eyeball, but nothing else to show for it.
    • There they go.

    This isn’t really your fault – it happens a LOT – studies show 7 out of 10 visitors to any site disappear without leaving a trace.
    But you CAN fix that.
    Web Visitors Into Leads is a software widget that’s works on your site, ready to capture any visitor’s Name, Email address and Phone Number. It lets you know right then and there – enabling you to call that lead while they’re literally looking over your site.
    CLICK HERE http://jumboleadmagnet.com to try out a Live Demo with Web Visitors Into Leads now to see exactly how it works.
    Time is money when it comes to connecting with leads – the difference between contacting someone within 5 minutes versus 30 minutes later can be huge – like 100 times better!
    Plus, now that you have their phone number, with our new SMS Text With Lead feature you can automatically start a text (SMS) conversation… so even if you don’t close a deal then, you can follow up with text messages for new offers, content links, even just “how you doing?” notes to build a relationship.
    Strong stuff.
    CLICK HERE http://jumboleadmagnet.com to discover what Web Visitors Into Leads can do for your business.
    You could be converting up to 100X more leads today!
    Eric
    PS: Web Visitors Into Leads offers a FREE 14 days trial – and it even includes International Long Distance Calling.
    You have customers waiting to talk with you right now… don’t keep them waiting.
    CLICK HERE http://jumboleadmagnet.com to try Web Visitors Into Leads now.
    If you’d like to unsubscribe click here http://jumboleadmagnet.com/unsubscribe.aspx?d=ayanokoujimonki.top

  23. Eric Jones
    10月前
    2023-8-16 7:52:04

    Dear ayanokoujimonki.top Owner. my name’s Eric and I just ran across your website at ayanokoujimonki.top…
    I found it after a quick search, so your SEO’s working out…
    Content looks pretty good…
    One thing’s missing though…
    A QUICK, EASY way to connect with you NOW.
    Because studies show that a web lead like me will only hang out a few seconds – 7 out of 10 disappear almost instantly, Surf Surf Surf… then gone forever.
    I have the solution:
    Web Visitors Into Leads is a software widget that’s works on your site, ready to capture any visitor’s Name, Email address and Phone Number. You’ll know immediately they’re interested and you can call them directly to TALK with them – literally while they’re still on the web looking at your site.
    CLICK HERE https://advanceleadgeneration.com to try out a Live Demo with Web Visitors Into Leads now to see exactly how it works and even give it a try… it could be huge for your business.
    Plus, now that you’ve got that phone number, with our new SMS Text With Lead feature, you can automatically start a text (SMS) conversation pronto… which is so powerful, because connecting with someone within the first 5 minutes is 100 times more effective than waiting 30 minutes or more later.
    The new text messaging feature lets you follow up regularly with new offers, content links, even just follow up notes to build a relationship.
    Everything I’ve just described is extremely simple to implement, cost-effective, and profitable.
    CLICK HERE https://advanceleadgeneration.com to discover what Web Visitors Into Leads can do for your business, potentially converting up to 100X more eyeballs into leads today!
    Eric
    PS: Web Visitors Into Leads offers a FREE 14 days trial – and it even includes International Long Distance Calling.
    You have customers waiting to talk with you right now… don’t keep them waiting.
    CLICK HERE https://advanceleadgeneration.com to try Web Visitors Into Leads now.
    If you’d like to unsubscribe click here http://advanceleadgeneration.com/unsubscribe.aspx?d=ayanokoujimonki.top

  24. Eric Jones
    10月前
    2023-8-15 23:46:24

    To the ayanokoujimonki.top Webmaster!
    My name’s Eric and I just found your site ayanokoujimonki.top.
    It’s got a lot going for it, but here’s an idea to make it even MORE effective.
    Web Visitors Into Leads – CLICK HERE http://jumboleadmagnet.com for a live demo now.
    Web Visitors Into Leads is a software widget that’s works on your site, ready to capture any visitor’s Name, Email address and Phone Number. It signals you the moment they let you know they’re interested – so that you can talk to that lead while they’re literally looking over your site.
    And once you’ve captured their phone number, with our new SMS Text With Lead feature, you can automatically start a text (SMS) conversation… and if they don’t take you up on your offer then, you can follow up with text messages for new offers, content links, even just “how you doing?” notes to build a relationship.
    CLICK HERE http://jumboleadmagnet.com to discover what Web Visitors Into Leads can do for your business.
    The difference between contacting someone within 5 minutes versus a half-hour means you could be converting up to 100X more leads today!
    Eric
    PS: Studies show that 70% of a site’s visitors disappear and are gone forever after just a moment. Don’t keep losing them.
    Web Visitors Into Leads offers a FREE 14 days trial – and it even includes International Long Distance Calling.
    You have customers waiting to talk with you right now… don’t keep them waiting.
    CLICK HERE http://jumboleadmagnet.com to try Web Visitors Into Leads now.
    If you’d like to unsubscribe click here http://jumboleadmagnet.com/unsubscribe.aspx?d=ayanokoujimonki.top

  25. Kam Kiefer
    10月前
    2023-8-11 10:13:47

    Hi, I’m sending you this message via your contact form on your website at ayanokoujimonki.top. By reading this message you’re living proof that contact form advertising works! Do you want to blast your ad to millions of contact forms? Maybe you prefer a more targeted approach and only want to blast our ad out to websites in certain business categories? Pay just $99 to blast your ad to 1 million contact forms. Volume discounts available. I have more than 35 million contact forms. Let’s get the conversation started, contact me via Skype here: live:.cid.83c9da999a4f9f

  26. Eric Jones
    10月前
    2023-8-10 22:32:33

    Hello ayanokoujimonki.top Webmaster.
    My name is Eric and unlike a lot of emails you might get, I wanted to instead provide you with a word of encouragement – Congratulations
    What for?
    Part of my job is to check out websites and the work you’ve done with ayanokoujimonki.top definitely stands out.
    It’s clear you took building a website seriously and made a real investment of time and resources into making it top quality.
    There is, however, a catch… more accurately, a question…
    So when someone like me happens to find your site – maybe at the top of the search results (nice job BTW) or just through a random link, how do you know?
    More importantly, how do you make a connection with that person?
    Studies show that 7 out of 10 visitors don’t stick around – they’re there one second and then gone with the wind.
    Here’s a way to create INSTANT engagement that you may not have known about…
    Web Visitors Into Leads is a software widget that’s works on your site, ready to capture any visitor’s Name, Email address and Phone Number. It lets you know INSTANTLY that they’re interested – so that you can talk to that lead while they’re literally checking out ayanokoujimonki.top.
    CLICK HERE http://jumboleadmagnet.com to try out a Live Demo with Web Visitors Into Leads now to see exactly how it works.
    It could be a game-changer for your business – and it gets even better… once you’ve captured their phone number, with our new SMS Text With Lead feature, you can automatically start a text (SMS) conversation – immediately (and there’s literally a 100X difference between contacting someone within 5 minutes versus 30 minutes.)
    Plus then, even if you don’t close a deal right away, you can connect later on with text messages for new offers, content links, even just follow up notes to build a relationship.
    Everything I’ve just described is simple, easy, and effective.
    CLICK HERE http://jumboleadmagnet.com to discover what Web Visitors Into Leads can do for your business.
    You could be converting up to 100X more leads today!
    Eric
    PS: Web Visitors Into Leads offers a FREE 14 days trial – and it even includes International Long Distance Calling.
    You have customers waiting to talk with you right now… don’t keep them waiting.
    CLICK HERE http://jumboleadmagnet.com to try Web Visitors Into Leads now.
    If you’d like to unsubscribe click here http://jumboleadmagnet.com/unsubscribe.aspx?d=ayanokoujimonki.top

  27. Eric Jones
    10月前
    2023-8-09 0:39:51

    Dear ayanokoujimonki.top Admin. I just found your site, quick question…
    My name’s Eric, I found ayanokoujimonki.top after doing a quick search – you showed up near the top of the rankings, so whatever you’re doing for SEO, looks like it’s working well.
    So here’s my question – what happens AFTER someone lands on your site? Anything?
    Research tells us at least 70% of the people who find your site, after a quick once-over, they disappear… forever.
    That means that all the work and effort you put into getting them to show up, goes down the tubes.
    Why would you want all that good work – and the great site you’ve built – go to waste?
    Because the odds are they’ll just skip over calling or even grabbing their phone, leaving you high and dry.
    But here’s a thought… what if you could make it super-simple for someone to raise their hand, say, “okay, let’s talk” without requiring them to even pull their cell phone from their pocket?
    You can – thanks to revolutionary new software that can literally make that first call happen NOW.
    Web Visitors Into Leads is a software widget that sits on your site, ready and waiting to capture any visitor’s Name, Email address and Phone Number. It lets you know IMMEDIATELY – so that you can talk to that lead while they’re still there at your site.
    You know, strike when the iron’s hot!
    CLICK HERE http://advanceleadgeneration.com to try out a Live Demo with Web Visitors Into Leads now to see exactly how it works.
    When targeting leads, you HAVE to act fast – the difference between contacting someone within 5 minutes versus 30 minutes later is huge – like 100 times better!
    That’s why you should check out our new SMS Text With Lead feature as well… once you’ve captured the phone number of the website visitor, you can automatically kick off a text message (SMS) conversation with them.
    Imagine how powerful this could be – even if they don’t take you up on your offer immediately, you can stay in touch with them using text messages to make new offers, provide links to great content, and build your credibility.
    Just this alone could be a game changer to make your website even more effective.
    Strike when the iron’s hot!
    CLICK HERE http://advanceleadgeneration.com to learn more about everything Web Visitors Into Leads can do for your business – you’ll be amazed.
    Thanks and keep up the great work!
    Eric
    PS: Web Visitors Into Leads offers a FREE 14 days trial – you could be converting up to 100x more leads immediately!
    It even includes International Long Distance Calling.
    Stop wasting money chasing eyeballs that don’t turn into paying customers.
    CLICK HERE http://advanceleadgeneration.com to try Web Visitors Into Leads now.
    If you’d like to unsubscribe click here http://advanceleadgeneration.com/unsubscribe.aspx?d=ayanokoujimonki.top

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