BioMoo Held on 19 Feb 1999

ClareS turns the ClareS_recorder on.

Gmocz [to ClareS] 1 pm

ClareS says "Hi, welcome to this PPS tutorial session..."

ClareS says "there is a choice of agendas today ;)"

ClareS says "we can either discuss web-publishing..."

ClareS says "... or, as it's the last session before "self-assessment", we can discuss any aspect of the course so far you have questions about"

ClareS says "anyone like to start with a question?"

Gmocz says " What is the next (self assasment) session about? Are we going to write a test?"

ClareS says "I will be mailing the list with full details early next week... but I guess you deserve a preview ;)"

ClareS says "it's a break between the semesters & a\ chance for you to find out how you're getting on understanding the material... but none of it contributes to the exam, hence "self" assessment"

ClareS says "there are two types of exercise"

ClareS says "quizzes, which are multi-choice on the web - you get instant feedback"

ClareS says "and short answer questions"

ClareS says "you will be expected to send the answers of those to your *group tutor* in the next 3 weeks"

ClareS says "and they will be marked - we will also have a couple of bioMOOs to go through the questions"

ClareS says "is that OK?"

Gmocz [to ClareS] Thank you. It is OK

JohnN says "Fine"

ClareS says "one of the main things about the short answer qs is that we expect *short* answers: not essays ;)"

Fulvio says "sorry, I dont know who my group tutor is?"

ClareS [to Fulvio] you should have been sent a mail message about this

Gmocz [to ClareS] I have the same question. Who is my group tutor?

ClareS says "if you haven't been it's Birkbeck's admin which has slipped up: sorry"

ClareS says "we will make sure that everyone knows this early next week"

JohnN says "I haven't looked at my e-mail lately!"

Fulvio says "I received only the password and user for the material, n"I received only the password and the userid"

Fulvio says "sorry for the bis[C[C[C[C[C[C[C[C[C"

JohnN says "Could I ask a question about chime 2?"

Gmocz says " I was searching the web for Ramachandran plot and found PPS course material from a previous class. Is earlier course material released to the public?"

ClareS says "it's important that everyone keep up with their email if possible: it's the most reliable way we have of contacting you"

ClareS [to JohnN] of course - go ahead

JohnN says "Using Chime-2, is there a way of replicating Rasmol commands such as*restrict* and *restrict within(6.0,Fe)* to allow one to focus a small part of the molecule-ligand binding or active siteor restrict/select residue 35-72?"

ClareS [to gmocz] last year's course material is restricted, the material before that is open access

ClareS [to gmocz] but surely there is a Ramachandran plot in this year's material...

JohnN [to ClareS] Sorry I've been away for a few days.

ClareS [to JohnN] I don't know - but I think so. The aim was to reproduce all the features of Rasmol with Chime2 and add some...

ClareS says "... but I only have Chime 1 here :("

Gmocz [to ClareS] Thank I know there is one.

ClareS [to JohnN] everyone goes away - and has flu - don't worry about it just catch up with email when you can

JohnN says "Could i ask what CpG is?"

ClareS [to JohnN] it's a dinucleotide - Cytosine then a sugar-phosphate backbone link (represented as p) then a Guanine

JohnN says "If it occurs in a sequence why isn't it just written CG?"

ClareS [to JohnN] usually people use that representation to talk about very short sequences (a couple of nucleotides) not bits of DNA

ClareS [to JohnN] what is the exact context in which it is mentioned?

JohnN says "I"

ClareS says "by the way I've just checked - not one of you is in my tutor group. You wil therefore each of you have either David Moss or Jim Pitts as a tutor - there are three groups this year"

JohnN says "Clusters of CpG's seem to indicate promoter regions in eukaryotic mRNA and Henri gives some explanation of why they are fo8und"

ClareS says "ah - then he could just as easily have written "CG", he just didn't"

ClareS says "you could write a whole DNA sequence putting the ps in meaning a sugar phosphate link each time, but it'd be a bit ugly & difficult to read the sequence"

ClareS says "and it goes without saying in DNA"

JohnN says "Thanks"

JohnN says "In section 4 mention was made of an article by Walter Gilbert on*the likely reason why eukaryotes have their genes *in pieces*,could someone give me the reference?"

ClareS [to JohnN] not off hand... sorry

Gmocz [to JohnN] In the past people sometimes used this notation CpG or CpGpApT etc but frequently anymore

ClareS says "I'll have a dig around in Medline and if I find the right reference I'll pot the list.. or you could, if you'd prefer?"

JohnN says " I'd like to read more about protein/DNA receptor contacts, so far I've only read Branden and Tooze 1991, could someone give me a more up-to-datereference?"
ClareS . o O ( post the list )

JohnN says "Thanks will do"

ClareS says "there is a new edition of Branden & Tooze published last year & very significantly expanded"

ClareS says "I am sure there is a long section on protein/DNA contacts"

ClareS says "it even has a CDROM"
ClareS is going to be reviewing it for the next issue of Biochemical Education

ClareS says "do you know the Current Opinion series of review journals?"

JohnN [to ClareS] Are you sure it is now published?

ClareS [to JohnN] if you mean B&T, I have been assured that my review copy is now in the ppost ;)
ClareS can't type

Fulvio says "In italy we are trying to buy it but it is not already available"
ClareS . o O ( I wonder why it's available here but not in Italy )

ClareS [to Fulvio] you mean in English, not the italian translation?

Fulvio says "Of course"

ClareS [to Fulvio] you could try the Internet bookshop

Gmocz [to Fulvio] You might want to try

JohnN says "I've enquired here a month or two ago and it had not been heard of by my book shop then"

ClareS says "maybe it's just out for review?"

Fulvio says "I mean that is not possible to buy it in Rome because of our bookstore"

ClareS says " might have it first ;)"
ClareS . o O ( great minds think alike )

Gmocz [to Fulvio] In December, they advertised the new TB is coming

ClareS [to gmocz] TB?

Gmocz [to ClareS] I mean Tooze & Branden
ClareS . o O ( Branden & Tooze... *that's* what confused me )

Gmocz [to ClareS] or the other way around

Gmocz says "I have a question about the Ramachandran plot. Is phi defined at all for the N-terminal, and similarly, is psi defeined for the C-terminal? If yes, how can they be calculated at the terminals?"

ClareS says "no, the phi & psi angles are never calculated for the terminal residues"

Gmocz [to ClareS] That was my feeling too, but I wanted some confirmation, to be sure. It is a kind of meaningless at the terminal. Thanks.

ClareS says "if you look at a calculated list of phis & psis (something that is rarely done now) you will see no entries for the terminal residues"

Gmocz [to ClareS] Usually I just see a plot but never had the chance to see a list

ClareS says "the plots are more useful than the lists unless you want to look at an individual residue"

ClareS says "in some cases any residues lying outside the most favoured regions (apart from Gly) are labelled"

ClareS says "it depends on the software that is used"

ClareS says "but in any case if you tried to label every residue of a plot it would get far too cluttered"

ClareS says "so there are cases where lists would be useful..."

Gmocz [to ClareS] Is public *source* for Ramachandran calculation available?

ClareS says "but you can also use rasmol to calculate properties (as long as you're using at least version 2.6)"

ClareS [to gmocz] yes...

ClareS says "there is a program called Procheck (available on the University College London server, I think) which will calculate it for any PDB file"

ClareS says "I think that the source of Procheck is public but I'm not sure and anyway you will have to ask for it"

Gmocz [to ClareS] I mean the promgram source in C or other language?

ClareS says "there is a very elderly program written in Fortran somewhere on the PDB server"

ClareS says "you could try and explore the Procheck site & see if it says anything about source code"

Gmocz [to ClareS] I will try it

Gmocz says "I was reading the Wednesday transcript, particularly the refolding part. If chaperonins are required for correct folding, how do we know that the final folded state is in absolute energy minimum, and not in a favorable local minimum to which it was directed or driven with the energy- using (ATP) chaperonins?"

Fulvio says "I think that an analisys of such type should be possible with SwissPDB viewer too"

ClareS says "I don't know that you can, the "correct" fold is only one of a population with quite similar energies"

Gmocz [to ClareS] Yes, but is that population somwhere close to the absolute minimum?

ClareS says "and of course proteins have kinetic energy - they're not at absolute zero so a "snapshot" of a protein at a particular time will not represent the absolute-zero minimum"

ClareS says "the lowest-energy state of a protein may well depend subtly (or even not so subtly) on conditions, like whether there is a ligand bound"
ClareS . o O ( is that clear enough? )

Gmocz [to ClareS] It is clear butIf chaperonins are required, how realistic is to model protein folding without accounting for chaperonins?

ClareS says "the protein fold must be stable in the absence of chaperonins"

ClareS says "it's still computationally impossible to model the protein folding pathway for a whole protein"

ClareS says "it is more possible to model the *folded* protein, which is stable without chaperonins"

Fulvio says "Does not molecular dynamic miic an unfolding process?"

ClareS says "not really, it mimics protein motion about a population of stable states"

ClareS would like to end the formal meeting soon it's getting very late (here) Gmocz [to ClareS"]: It seems to me that large proteins cannot be easily refolded after denaturation (unlike some smaller ones) Do you think, we will heve a method one day to easily refold any protein?

ClareS [to gmocz] are you talking experimentally or in simulation?

Gmocz [to ClareS] This time, EXPERIMENTALLY
ClareS is not an experimentalist.. quite probably?

Gmocz [to ClareS] I am not so sure. Wiith large protein it semms hopless in laboratory. But who knows...

ClareS says "I was just going on the theory that so many things seemed experimentally hope;less only a few decades ago. The human genome project, for instance ;)"

Fulvio [to gmocz] What you mean as large protein?

ClareS [to gmocz] I'm curious.. I've not looked into this. Is there a correlation between the ease with which a denatured protein re-folds and the number of domains?
ClareS . o O ( it would seem logical )

Gmocz [to Fulvio] Mw 50,000-2,000.000[D[D[D[D[D[D[D[D[D[D[D[D[D[D0,000-2,000,000

Gmocz [to Fulvio] -2,000,000

Gmocz [to ClareS] It could be. Multidomaiin enzymes can refold very badly to have activity again

JohnN says "Goodnight folks"
ClareS is

Fulvio says "I think that depend also from which denaturating strategies you aopply"
(JohnN has disconnected.)
ClareS is yawning

Gmocz [to Fulvio] Of course

ClareS says "I think it's about time to call a halt to the formal meeting. Goodnight and thanks for an interesting discussion!"
ClareS turns the ClareS_recorder off.