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MUD transcript:  10-12-99

Primary Structure of Proteins

Course room(s): PPS 

22:59:20  LarryT connects.

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22:59:24  DavidM connects.
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23:00:22  ClareS connects.
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23:00:30  ClareS says "Hello"
23:00:33  RamananS connects.
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23:00:54  ClareS says "sorry if I'm a couple of minutes late - but that's not unusual"
23:01:17  ClareS says "I'll wait a few minutes before starting properly to give others a chance to arrive"
23:03:55  LesleyM connects.
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23:05:37  ClareS says "Hi - welcome! I'd like to start the meeting now... by thanking you all for turning up"
23:06:18  LesleyM says "hi Clare, I think I' connected."
23:06:41  DavidM says "Hello, Clare"
23:07:26  ClareS says "Hi again, sorry I lost the connection for a minute then"
23:07:42  ClareS says "how are you getting on with the course so far?"
23:07:43  LesleyM says "Are we supposed to be discussing any thing in particular this session?"
23:08:16  ClareS says (to lesleym) "only the first two sections of the course material!"
23:08:50  ClareS says (to lesleym) "they're quite straightforward ones, so this is also another opportunity for you to learn about the MUD"
23:09:15  ClareS says "but if any of you have any particular questions you'd like to ask, go ahead..."
23:09:41  LesleyM says "well that's quite a bit. I have a question re Implications of Primary Structure Material. What is meant by "resonable allowance for insertions and deletions"?"
23:10:17  ClareS says (to lesleym) "could you post the URL, please? I'd like to look at the context"
23:11:41  LesleyM says (to say) "cryst.bbk.ac.uk/ppscore/section2/implications.shtml"
23:12:34  ClareS says (to lesleym) "thanks!"
23:14:21  ClareS says (to lesleym) "I've found that section now... it means that, if you have two proteins that are (very approx.) 15-25% identical..."
23:15:04  ClareS says "... so that you are not sure from identity alone whether they are homologous (evolutionarily related) or not..."
23:15:41  ClareS says "... they are more likely to be related if there are few insertions or deletions in one protein relative to the other"
23:15:52  RamananS disconnects.
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23:15:59  ClareS says "you might have two proteins of very different lengths where one section is quite similar"
23:16:30  ClareS says "in that case you may well have a conserved domain but the proteins wouldn't (necessarily) have the same overall structure"
23:16:38  ClareS says "does that make sense?"
23:16:57  ClareS looks at david for confirmation
23:19:06  RamananS connects.
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23:19:13  LesleyM says "I think it does. Let me see - two proteins with longish identical sections would be thought of as homologous even if there were then some significant insertions/deletions upto 20%.?"
23:19:55  ClareS says "not quite... I don't think I've explained it very clearly"
23:20:11  ClareS says "you have 2 proteins about 20% identical..."
23:20:48  ClareS says "if the similarity is spread over the whole length of the protein, with few long gaps, they are (most) likely to be (distant) homologs"
23:21:23  ClareS says "if one or more sections are well conserved but there are long gaps with few identities..."
23:21:51  ClareS says "... I'd say it was less likely that the proteins were directly related tho' they will certainly share one or more structural or functional domains"
23:22:17  ClareS says "(e.g. an immunoglobulin domain, or a tyrosine kinase domain"
23:22:28  ClareS says "is that clearer?"
23:22:38  ClareS must remember to close brackets
23:23:32  LesleyM says "I think I get the idea but may be fixing too much on the 20% value - where does that come from? Is it empirical, statistical or what?"
23:23:51  DavidM says "If the 15-20% identity is uniformly spread then there is less likely to be an evolutionary relationship than if there are insertions of lower homology and longer regions of higher homology"
23:24:27  DavidM says "That is what Clare is saying, I think!"
23:24:45  ClareS says "the 20% is empirical -- it just turns out to be a useful cut-off. It won't apply in all situations"
23:25:17  ClareS says (to davidm) "you've explained it clearer than I did"
23:25:39  LesleyM says "OK - I can see that. When might it not apply?"
23:25:52  ClareS says "tho' proteins which are 20% identical with uniform identity are quite likely to be distantly related"
23:26:37  LesleyM says "sorry to hog all your time. I am clearer now."
23:26:43  DavidM says "Ther is a paper by Mike Sternberg in J Mol Biol, 1999 which looks at homologous sequences of low identity. I haven't got the reference here. Clare knows the paper."
23:26:48  ClareS says "you take a family like the globins -- some globins are only about 15% identical but this is a very clear evolutionarily related family"
23:26:48  RamananS says "thanx wizard pages;Learning a lot already watching you guys talk"
23:27:12  ClareS says "some proteins with that degree of identity are not related at all"
23:27:42  ClareS says "particularly proteins that have slightly odd compositions, e.g. coiled coils contain a high proportion of certain amino acids"
23:27:57  ClareS says "you will then get quite high identities "by chance""
23:28:08  LesleyM says "Is the J Mo Biol paper useful in illustrating these differences?"
23:28:31  ClareS is looking up the full reference in medline
23:29:10  ClareS says "you can probably trust mike sternberg more than either david or me on this, he's studied this problem for many years"
23:29:29  DavidM says "I will look at the paper again and if it is relevant we can email the reference"
23:29:36  LesleyM says "will look it up"
23:30:46  LesleyM says "another question - how much should we know/be able to relate re chemical techniques for sequencing?"
23:32:17  ClareS says "The paper David was referring to must be J Mol Biol. 1999 Nov 12;293(5):1257-1271"
23:32:43  ClareS says "the title is "Benchmarking PSI-BLAST in Genome Annotation""
23:33:07  LesleyM says "thank you"
23:33:11  ClareS says "http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?uid=10547299&form=6&db=m&Dopt=b"
23:33:34  ClareS says "sorry, I don't think that that link is fully clickable"
23:34:02  DavidM says "Mike looks at the ability of PSI-BLAST to pick up homologies at low sequence identity"
23:34:16  ClareS says "there are statistical tests for working out whether two proteins are similar enough to be definitely related, that take sequence composition into account"
23:34:57  ClareS says "is that clear (more or less)?"
23:35:17  LesleyM says "is this PSI_BLAST statistical?"
23:36:03  ClareS says (to lesleym) "it uses statistical techniques to list sequences in order of probability of homology (if that makes sense?)"
23:36:34  LesleyM says "yes, I think it's clear. Many thanks."
23:36:37  ClareS says "all programs for searching databases with sequences do that"
23:37:21  ClareS says "the difference with PSI-blast is that it is iterative - it creates an alignment of related sequences from the first search"
23:37:34  ClareS says "and goes on to re-search the database with that alignment"
23:38:45  DavidM says "We will come back to sequence alignment in the bioinformatics part of the course"
23:39:23  ClareS says (to davidm) "I don't think Terri's exercise includes PSI-blast: can you remember whether it does?"
23:39:34  LesleyM says "I leave it for now - need to look at that paper"
23:40:07  ClareS says "bioinformatics (mostly sequence alignment) is covered quite extensively in section 5 of the course"
23:40:25  ClareS says "you'll come on to that in late January - the second section of the new year"
23:40:26  RamananS says "would the course cover how these databases work in more detail at some stage in 99/00"
23:40:39  ClareS got there before Ramanan ;)
23:42:35  ClareS just lost the connection for a couple of seconds again
23:43:01  RamananS says "this is great ;can I diturb and ask questions on problems telnetting"
23:44:22  ClareS says (to ramanans) "of course - go ahead"
23:44:29  RamananS says "I figured it out ;the port no. was wrong sorry!"
23:44:54  ClareS says "it is *very* important to get the port no. right ;)"
23:45:21  ClareS says ".. and to remember that the port no. for telnet to the MUD is not the same as for the HTTP interface"
23:45:53  ClareS says "bioinformatics is probably the most popular part of the course, at least at the moment"
23:46:08  LesleyM says "please jump in when you want Ramanan"
23:46:52  RamananS says "Sorry I've been not upto it totally.But will catch up by the next MUD session."
23:46:58  DavidM says "The port numbers over 1024 are used for special purposes such as MUDs"
23:46:58  LesleyM says "about the chemical method of sequencing - how much is it advisable to know?"
23:47:43  DavidM says "The low numbers are all standardized. So 80 is for HTTP (eg browsers) and 23 is for telnet"
23:47:56  ClareS says (to lesleym) "sorry, I didn't answer that question earlier - it arrived in the middle of our long discussion of distant homology"
23:48:21  RamananS says "i haven't looked at the released material in detail yet;can you recommend a good e-journal searching program"
23:48:37  ClareS says "it is not necessary for you to know a great deal about chemical sequencing - in fact I can't remember a single mention of it in the course"
23:48:45  ClareS says (to davidm) "can you?"
23:49:18  DavidM says "We are developing another Adv Cert with that sort of thing in it"
23:50:38  LesleyM says "there is brief mention in 3.5 sequencing (talk of 6N HCl...) for cleavages.."
23:50:41  ClareS says "if you complete PPS and then that new course (probably not available until some time in 2001) we hope that you may be eligible for an M.Sc."
23:50:52  ClareS says "we are currently working out most of the details"
23:51:27  ClareS says (to lesleym) "you don't need to know about how the sequencing is performed, tho'"
23:52:20  LesleyM says "the new cert also sounds quite appealing (slushy stuff for a change)"
23:52:21  RamananS says "Isn't general sequencing totally automated yet?"
23:52:21  ClareS says (to ramanans) "do you know BioMedNet?"
23:52:33  ClareS says "http://www.biomednet.com"
23:52:56  ClareS says "if any of you are not yet members of biomednet it's well worth joining - and it's free"
23:53:34  ClareS says "you get access to full evaluated Medline, and if *your institution* has bought the paper version of a journal you may be able to see the full text online for free"
23:53:57  ClareS says "even if you don't have access you can buy an individual article for a few dollars with a credit card"
23:54:05  RamananS says "are their any other servers/resources that we have access to with the bbk passwords"
23:54:28  ClareS says "not with the PPS passwords"
23:55:33  ClareS says (to lesleym) "it's all the theory behind the techniques, we can't teach practical mol. biol. online (yet ;)"
23:55:50  DavidM says "I was thinking about that. We will have to check this with our librarian"
23:56:10  RamananS says "I am sorry what I meant was ,do we have free access too any other resources that one would be expected to pay otherwise"
23:56:27  ClareS says (to ramanans) "most protein sequences these days are obtained by translating gene sequences - obviously gene sequencing is now automatic and very fast"
23:57:07  ClareS says "the only difficulty is that the programs available for predicting gene locations are still quite crude"
23:57:23  LesleyM says (to ClareS) "yes that would be a problem!"
23:57:47  ClareS says "david was saying that we will check with Birkbeck's library staff whether you can have access to the online services provided via Birkbeck's library"
00:01:00  LesleyM says (to ClareS) "I have purchased Voek & Voek, plus Branden a& Tooze. Should this suffice for basic texts?"
00:01:27  ClareS says (to lesleym) "Yes, I should think so!"
00:01:53  ClareS says (to lesleym) "(assuming that you mean Voet & Voet - I've never heard of a textbook author called Voek ;)"
00:02:09  DavidM says "There is Voet, Voet and Pratt which has a CD-ROM with it and is very good"
00:03:08  LesleyM says (to ClareS) "yes that's the one although sans CD (I'over CDed anyway for now)"
00:03:29  ClareS says "that is the newer edition of Voet & Voet - they acquired another co-author when they brought out the CD"
00:04:11  ClareS says "I think I must go quite soon: I am beginning to fall asleep at the keyboard. Are there any final questions?"
00:04:59  DavidM says "Does everybody know that the Birkbeck network is going to be down this weekend"
00:05:01  RamananS says "what's Prat all about?Strucural biology....?"
00:05:03  ClareS looks round expectantly
00:05:17  LesleyM says "I will leave you all to your slumbers now - sleep well and many thanks!"
00:05:35  ClareS says (to ramanans) "I'm not quite sure what you mean?"
00:06:03  ClareS says "yes, David has made a good point: please remember to log off when you leave the MUD and don't try too hard to look at the course over the weekend"
00:06:12  ClareS says "our server is being upgraded"
00:06:14  DavidM says "Quite alot of V,V and P is about structural biology in the biochemical context"
00:07:06  RamananS says "I get it good old voet ,voet and Pratt.I have nop more stupid Qs;Good night everyone"
00:07:29  LesleyM waves goodbye
00:08:03  ClareS yawns
00:08:05  DavidM waves
00:08:07  LesleyM disconnects.
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00:08:07  LesleyM connects.
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00:08:12  LarryT disconnects.
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00:08:23  ClareS says (to davidm) "thank you for helping me out with some of the questions ;)"
00:08:47  DavidM says "Thank you Clare"
00:09:02  DavidM says "Bye"
00:09:15  ClareS waves goodnight
00:09:28  ClareS disconnects.