BioMoo Held on 17 Feb 1999

ClareS turns the ClareS_recorder on.
Geraint finds his way in.
ClareS is ready to go at long last...
(Geraint has disconnected.)
KLaurio waves at geraint

KLaurio says "missed him/her... :("
ClareS . o O ( geraint is also having problems with the connection? )

ClareS says "Hi, welcome to this PPS meeting (in spite of the connection problems)"
Roby . o O ( a bumpy day? )

KLaurio says "is the recorder on?"

ClareS says "we will be discussing Web Publishing (from a biochemical point of view ;) and also anything else you're having problems with in this last session before the mid-semester break"

ClareS [to KLaurio] yes, but could you still please send me a transcript

KLaurio [to ClareS] ok, will do

ClareS [to KLaurio] thanks...

ClareS says "does anyone want to start off with a question?"

KLaurio says " i don't have questions about www publishing, so someone else can go first..."
AndyS finds his/her way in.

Roby says "The section says you do not have a way of changing a font when doing HTML stuff. Is that exactly so? I thought you have the chance to choose any font you want ... "

AndyS says "sorry I'm late"

Roby says "of course, from a biochemical point of view :)"

ClareS says "there is a distinction between "standard HTML" and Netscape extensions"

ClareS says "in standard HTML (even v. 3 I think, tho' I can't be absolutely sure about this) there is no possibility to change font"

ClareS says "you are stuck with what the user sets as default font for proportional and non-proportional spacing"

ClareS says "Netscape has introduced the ClareS says "is that clear?"
The housekeeper arrives to cart Geraint off to bed.

ClareS says "in *basic* HTML, you are not expected to use these extensions as not everyone will be able to see the different fonts. But very, very many people do"

AndyS says "the font face= also works in IE"

Roby says "How's that, so there is no difference between them?"

ClareS says "Few people remember this, but Netscape and IE are not the only two browsers on the planet"

AndyS says "really!!"
ClareS . o O ( tho' they do have about 95% of the market between them )

ClareS says "it is true that IE uses Netscape's extensions"

ClareS says "but there *are* still browsers which don't (or can't)"

ClareS says "the only other one I can think of off hand is Lynx - a text only browser which can be quite useful on occasions"

AndyS says "How?"

ClareS says "it's *still* good programming practice to make sure that your web pages can be read by people who are using text only browsers"
Fulvio finds his way in.

ClareS [to AndyS] by people coming in on very, very slow lines...

ClareS says "more often, of course people will just turn images off if the line is very slow"

Roby says "I can think of the AOL browser too, and Mosaic ..."

ClareS says "and there are few things more annoying than a web page which makes no sense at all unless a set of large images are loaded"

Fulvio says "hello to everyone"
ClareS remembers Mosaic. Well ;)

ClareS [to Fulvio] Hi

Roby says "hi"

KLaurio says "hi"

Roby says "that's true, very annoying ..."

ClareS says "there is another problem with using unusual fonts: they must be loaded on the client machine if they are to be visible"

ClareS says "and there's the problem of very similar fonts with different names for Windows and the Mac"
Geraint finds his way in.

ClareS [to Geraint] Hi - welcome

AndyS says "or they are invisible?"

Geraint says "Hello"

Fulvio says "Hi"

Roby says "hi"
KLaurio waves to geraint

ClareS [to AndyS] no, if the font isn't loaded on the user's machine the default font (proportional / non-proportional) is displayed instead

KLaurio says "I have a question on protein folding"

KLaurio says "after translation, how long does it take to collapse? ms, ns, ps?"

ClareS says "in Netscape 4 you use Edit / Preferences / Fonts to see what the default is"
ClareS is not really sure.. slower than ps.

KLaurio says "ok, also, the role of chaperones is a little unclear for me, how important are they for folding?"

ClareS says "very..."

Fulvio says "Folding is a process that follow the translation during its prosecution, I think."
ClareS . o O ( a useful comment )

KLaurio says "where do chaperones come from? do they have genes too?"

ClareS says "there's a lot of useful stuff on chaperonin on the Birkbeck pages: see"

ClareS [to KLaurio] yes.. *all* proteins (and specific RNAs) have genes...

ClareS says "another useful chaperonin resource is at"
ClareS . o O ( it's a US based site so is currently very slow )

KLaurio [to ClareS] ok, looking...
Geraint finds his way out.
ClareS thought there was a section on chaperonins later in the course but is not so sure now

KLaurio says "does a fresh AA sequence fold as easily back into its active fold as one that has been denatured?"

KLaurio says "does it have a 'memory'?"

ClareS says "interesting question.. one I'm not quite sure of the answer to"

ClareS says "I've never heard of a difference in folding times between new & denatured sequenes"
ClareS . o O ( sequences )
ClareS can't type

KLaurio says "could it be that the chaperones are needed in the very first folding"

KLaurio says "since many different sequences fold into the same structure (which is very confusing to me)"

Fulvio says "I dont know about the time, but surely refolding is a slow process that needs a lot of control, instead folding naturally occurred more or less at the same time of the traslation"
Geraint finds his way in.

ClareS says "one of the people at the cutting edge of research into protein folding is Sheena Radford at the University of Leeds"

ClareS says "her web server is at"

Geraint says "I'm sorry but getting this connection is proving very, very difficult today. Is anyone else having problems?"

Fulvio says "sometimes denatured proteins needs hours to refold"

KLaurio [to ClareS] thanks

ClareS [to Geraint] it's not too bad now but it was appalling earlier

KLaurio [to Fulvio] with or witout chaperones?

ClareS says "links from Sheena Radford's page under Electrospray Mass Spectrometry give an answer to the question asked at the beginning.. ms. Tens to thousands of ms"

ClareS says "(that's for *re-folding* of denatured lysozyme"

ClareS says ")"

Fulvio says "I know that chaperones increase the rate of refolding and protect a protein against denaturating agents"

KLaurio [to ClareS] ok, excellent

Fulvio says "there are a lot of paper from Creighton, Baldwin, Goto and so on on the subject"

KLaurio says "I saw in a previous transcript that you talked about modeling different aspects of amino acids for substitution matrices"

ClareS is having connection problems too (
(ClareS has disconnected.)
(ClareS has connected.)

ClareS says "I'm sorry, but my connection is proving very, very slow again"

ClareS [to KLaurio] yes, I seem to be back OK now, go on?

KLaurio says "several different 'contexts' of AAs can be captured in a Dirichlet mixture"

KLaurio says "where some model hydrophobic, some aromatic, some small, some charged etc."

KLaurio says "this is used in the training of HMMs"

Roby says "what does HMMs stand for?"

KLaurio says "HMM = hidden Markov models"

KLaurio says "where they are used to estimate they 'true' distribution behind the observed frequencies"

KLaurio says "just wanted to comment, since someone wrote it is impossible..."

ClareS says "you mean, without allowing for the bias caused by the fact that some proteins are easier to crystallise than others"

KLaurio says "of course, it is always based on the data that you estimate your mixture from, which can be biased :("

ClareS [to KLaurio] true...

ClareS [to Roby] hidden Markov models are now often used in bioinformatics programming - database searching, sequence alignment, pattern identification

KLaurio says "one last question, on protein engineering, is it done bottom up of top down? which would be the ideal method to design new proteins?"

Roby [to ClareS] thanks Clare ...

Geraint says "Does this mean that current HMM methods are biased toward soluble proteins and away from intrinsic membrane proteins as these are currently harder to get structures for?"

ClareS [to KLaurio] what do you mean exactly by bottom-up and top-down?

KLaurio [to ClareS] start with desired function->look for building block->assemble->test (top-down) or

KLaurio [to ClareS] start with known protein->tinker little->test?

ClareS says "both. Bottom up (start with known protein) is easier"

KLaurio [to Geraint] yes, they could be, you have to know how the people behind the scenes build their tools

ClareS says "you could say that site directed mutagenesis is a very simple form of bottom-up protein design"

ClareS says "you start with a known protein and change one or two amino acids to try to alter its properties"

ClareS [to Geraint] all methods which depend on analysis of known structures are biased against transmembrane proteins as there are so few structures

KLaurio says "to ClareS are there any tools that suggest which AAs you should change and how?"

ClareS [to KLaurio] you need to know as much as you can about the function of your particular protein. We're looking at the level of changing a few residues in the active site - first find your active site ;)

Fulvio says "There is a freely available tools that allow to evaluate the functionality of a mutated active site"

ClareS says "given the slow links I would like to close the meeting, in the next few minutes"

KLaurio [to ClareS] ok, thanks

ClareS says "thank you all for your patience with the speed and for asking such interesting questions"

KLaurio [to Fulvio] remember name/link?

Fulvio says "sorry, it was a question"

ClareS says "you can always post scientific questions to the list - and there's the 11pm MOO session on Friday "

KLaurio [to Fulvio] ok...

Fulvio [to KLaurio] if I find something I will post it to the list.
ClareS turns the ClareS_recorder off.