From owner-molec-model@net.bio.net Wed Sep 02 23:00:00 1998
Path: biosci!SLIP.NET!grizzly
From: grizzly@SLIP.NET (Michael Sherrell)
Newsgroups: bionet.molec-model
Subject: Sciex API III+ LC/MS/MS
Date: 2 Sep 1998 18:52:16 -0700
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Sciex API III LC/MS/MS available at an excellent price:
Vintage 1993
Upgraded to III+
API, ES, APCI sources
Mass range to 2400 amu
Always and currently under PE service contract
New price was $539,000; price now: $79,000
For more details, please give me a call.

Mike Sherrell
Grizzly Analytical (USA)
707 887 2919/fax 707 887 9834
www.grizzlyanalytical.com


From owner-molec-model@net.bio.net Wed Sep 02 23:00:00 1998
Path: biosci!NS1.NIMR.MRC.AC.UK!jsaldan
From: jsaldan@NS1.NIMR.MRC.AC.UK (Jose Saldanha)
Newsgroups: bionet.molec-model
Subject: [ANNOUNCE] Humanization bY Design WWW Site
Date: 3 Sep 1998 05:38:42 -0700
Organization: National Institute for Medical Research
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[ANNOUNCE] Humanization bY Design WWW Site

http://www.cryst.bbk.ac.uk/~ubcg07s
http://mathbio.nimr.mrc.ac.uk/jsaldan

The "Humanization bY Design" web site contains a background to antibody
humanization as well as discussing various issues concerning the
design of humanized antibodies for therapy and diagnosis. It includes
information on the majority of humanized antibodies that have been
published in the scientific literature. Text and sequence searching
facilities are provided to find the humanized antibody of interest.



From owner-molec-model@net.bio.net Thu Sep 03 23:00:00 1998
Path: biosci!news.stanford.edu!nntp.cs.ubc.ca!newsfeed.direct.ca!news-peer.sprintlink.net!news-backup-east.sprintlink.net!news.sprintlink.net!207.180.0.49!news.ici.net!not-for-mail
From: "Hilton Evans" <hfevans@ici.net>
Newsgroups: alt.sci.nmr,bionet.molec-model,de.sci.biologie,de.sci.chemie,ncsc.chemistry
Subject: Explore Molecular Geometry
Date: 4 Sep 1998 11:43:38 GMT
Organization: Chempen Software
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ChemPen Chemical Structure 
Drawing and Modeling Software
http://home.ici.net/~hfevans/chempen3d.htm

From owner-molec-model@net.bio.net Fri Sep 04 23:00:00 1998
Path: biosci!pravda.ucr.edu!awabi.library.ucla.edu!208.134.241.18!newsfeed.internetmci.com!144.212.95.13!nntprelay.mathworks.com!news.mathworks.com!uunet!uunet!in2.uu.net!news.ici.net!not-for-mail
From: "Hilton Evans" <hfevans@ici.net>
Newsgroups: bionet.molec-model,de.sci.chemie,sci.chem,sci.chem.labware,sci.chem.organomet,sci.engr.chem,sci.research
Subject: Molecular Mechanics
Date: 5 Sep 1998 15:53:14 GMT
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ChemPen3D Chemical Drawing and Modeling Software
http://home.ici.net/~hfevans/chempen3d.htm

-- 
Hilton Evans

From owner-molec-model@net.bio.net Sat Sep 05 23:00:00 1998
Path: biosci!agate!newsfeed.berkeley.edu!howland.erols.net!vixen.cso.uiuc.edu!dhardy
From: dhardy@students.uiuc.edu (david joseph hardy)
Newsgroups: bionet.molec-model
Subject: Announce: NAMD 1.5 released
Date: 6 Sep 1998 00:37:08 GMT
Organization: University of Illinois at Urbana-Champaign
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Announcing the release of NAMD version 1.5
------------------------------------------

The Theoretical Biophysics group of the Beckman Institute at the 
University of Illinois would like to announce the availability of 
version 1.5 of NAMD, a high-performance molecular mechanics program 
for simulating large biomolecular systems on parallel and distributed 
computers.  This software is being made available to the molecular 
modeling community free of charge and includes commented source code 
and extensive documentation.  

New in this version
-------------------
* Added features include rigid bonds and moving harmonic restraints.
* Updated user guide, also available in HTML form.  
* Modified to work with PVM 3.4 beta.  
* Enhanced performance by as much as 30%.  
* Modified to work with the latest version of DPMTA (2.7).  
* Included DPMTA source to make installation easier.  
* Simplified build process, fewer options to specify, better documentation.  
* Several bug fixes.  

====================  Basic information about NAMD  ======================

Obtaining NAMD
--------------
A more complete description of NAMD is available on the NAMD home page:
	http://www.ks.uiuc.edu/Research/namd/

The software itself is available via anonymous ftp in the directory:
	ftp://ftp.ks.uiuc.edu/pub/mdscope/namd/

Email questions to namd@ks.uiuc.edu.

Features
--------
Efficient full electrostatics:
  NAMD incorporates the Distributed Parallel Multipole Tree Algorithm
  (DPMTA) developed by the Scientific Computing Group at Duke University
  to provide full electrostatic interactions in O(N) time.  To further
  reduce the computational cost, DPMTA is integrated using a multiple
  timestep integration scheme which computes full electrostatic
  interactions only periodically during the simulation.

Scalable parallelism:
  NAMD has an efficient parallel design that allows large systems to 
  scale well to many processors.  The use of a spatial decomposition 
  scheme combined with message-driven execution achieves load balance 
  and the overlap of communication and computation.  

Modifiable:
  A major design goal of NAMD is to allow researchers to implement new 
  algorithms and techniques easily.  To achieve this, NAMD design and
  implementation is fully documented in the NAMD Programming Guide.  
  NAMD has an object-oriented design implemented in C++ to provide a 
  high degree of modularity and data abstraction.  

Portable:
  For communication, NAMD uses PVM (Parallel Virtual Machine) from 
  Oak Ridge National Laboratory, which has itself been ported to 
  most architectures.  Porting NAMD is then simply a matter of having 
  PVM and a reasonable C++ compiler.  We have successfully ported 
  NAMD to all of our UNIX machines, which include HP, SGI, Sun, 
  and Linux, both single processor and shared memory multiprocessor.  

Compatibility with X-PLOR:
  The input and output files used by NAMD are identical to those used 
  by the program X-PLOR.  Thus, simulations can be easily migrated 
  between the two packages, allowing the output of NAMD to be analyzed 
  using X-PLOR or any other tool built for these file formats.

Standard MD features:
  NAMD implements standard molecular dynamics features such as energy 
  minimization, velocity rescaling, spherical boundary conditions, 
  harmonic constraints, and Langevin dynamics.

Requirements
------------
* UNIX with C and C++ compilers.
* PVM (http://www.epm.ornl.gov/pvm/pvm_home.html).
* For generating required PSF structure files, we recommend 
  X-PLOR (http://xplor.csb.yale.edu/xplor-info/xplor-info.html).

==========================================================================
Theoretical Biophysics Group 
NIH Resource for Macromolecular Modeling and Bioinformatics 
Beckman Institute for Advanced Science and Technology 
University of Illinois at Urbana-Champaign 


						David Hardy
						namd@ks.uiuc.edu
						September 4, 1998

From owner-molec-model@net.bio.net Sat Sep 05 23:00:00 1998
Path: biosci!news.stanford.edu!Cabal.CESspool!bofh.vszbr.cz!news.maxwell.syr.edu!intgwpad.nntp.telstra.net!nsw.nntp.telstra.net!news.tig.com.au!not-for-mail
From: "sparky" <y115@hotmail.com>
Newsgroups: bionet.molec-model,comp.lang.modeling.gams,de.rec.modelle,de.rec.modelle.bahn,de.rec.modelle.misc
Subject: cool site
Date: Mon, 7 Sep 1998 00:09:03 +1000
Organization: The Internet Group Ltd
Lines: 13
Message-ID: <6su8ik$gdb$1@toto.tig.com.au>
NNTP-Posting-Host: p23-max16.syd.ihug.com.au
X-Newsreader: Microsoft Outlook Express 4.72.3110.22
X-MimeOLE: Produced By Microsoft MimeOLE V4.72.3110.22

hi...
this is a site where you can go if you stuck with something and you can not
find...just ask them...they'll search for it manually and display it for
you...even if you like to see a picture or anything..just ask...
go to :
http://homepages.tig.com.au/~georgeis/sparky/cube.htm.

bookmark it and send the address to your friends...
it's a diferent site...it's something else..





From owner-molec-model@net.bio.net Sun Sep 06 23:00:00 1998
Path: biosci!reading.ac.uk!l.r.cooper
From: l.r.cooper@reading.ac.uk (Lee Cooper)
Newsgroups: bionet.molec-model
Subject: gromos96
Date: 7 Sep 1998 03:33:39 -0700
Organization: pedal
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hello m-modellers,

anyone out there using gromos96 to model post-translational
modifications of proteins? any help is appreciated, answers will be
summarized and re-posted.

-- 
regards
lee
 ==================================================
\Mr. Lee R. Cooper Bsc(Hons), Dept. of Comp. Sci., \
\University of Reading,	Whiteknights PoBox 225,    \
\Reading, Berkshire. RG6 6AY (UK) Fax 0118 975 1994\
\Tel +44 (0)118 987 5123 x7645 (0915-1700)         \
\Tel +44 (0)118 931 8188 x7817 (1900-2300)         \
 ==================================================

From owner-molec-model@net.bio.net Sun Sep 06 23:00:00 1998
Path: biosci!IRIS.BIO.USTC.EDU.CN!zhouli
From: zhouli@IRIS.BIO.USTC.EDU.CN (Zhou Li)
Newsgroups: bionet.molec-model
Subject: about PLS
Date: 7 Sep 1998 06:44:40 -0700
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hi,modellers

Does anybody know about Partial Least Square algorithms?
Need you help.

--
Li Zhou
Graduate Student on SBDD ( Structure Based Drug Design )
Molecular Modelling Group  Laboratory of Structural Biology
Dept. of Cell and Molecular Biology  College of Life Sciences
Univ. of Science and Technology of China  Hefei  230027
P.R.China

From owner-molec-model@net.bio.net Sun Sep 06 23:00:00 1998
Newsgroups: bionet.biophysics,bionet.molec-model
Path: biosci!news.stanford.edu!nntp.cs.ubc.ca!newsfeed.direct.ca!news.idt.net!nntp2.cerf.net!nntp3.cerf.net!news.msi.com!uucp
From: "Jeffrey L. Nauss" <jnauss@usa.net>
Subject: Post-doc opening: molecular modeling of protein-DNA complexes
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	Unless stated otherwise, everything in this message is personal opinion
	and nothing in it is an official statement of Molecular Simulations Inc.
Lines: 25
Xref: biosci bionet.biophysics:4371 bionet.molec-model:2231

Molecular Simulations Inc. has an *immediate* opening for a
post-doctoral scientist to investigate the dynamics of topoisomerase I,
its complex with DNA, and possibly new drug candidates. The position
will involve extensive use of a variety of software packages being
developed here at MSI.

This position will be in our San Diego office and will last until April
1999.  If you know of anyone interested in this position, please have
them forward their resume and CV to me at the address shown below.

--
Jeffrey L. Nauss, PhD                                Phone: (619)
799-5555
Product Specialist, Simulations                    Fax: (619) 458-0136
Molecular Simulations Inc                           E-mail:
jnauss@msi.com
9685 Scranton Road
San Diego, CA 92121


 
 -disclaimer-
 unless stated otherwise, everything in the above message is personal opinion
 and nothing in it is an official statement of molecular simulations inc.

From owner-molec-model@net.bio.net Tue Sep 08 23:00:00 1998
Path: biosci!news.stanford.edu!su-news-feed2.bbnplanet.com!su-news-hub1.bbnplanet.com!cpk-news-hub1.bbnplanet.com!news.bbnplanet.com!portc02.blue.aol.com!audrey01.news.aol.com!not-for-mail
From: paraleepk@aol.com (Paralee PK)
Newsgroups: bionet.molec-model
Subject: 3-D structure of DNA
Lines: 20
Message-ID: <1998090904080000.AAA18636@ladder01.news.aol.com>
NNTP-Posting-Host: ladder01.news.aol.com
X-Admin: news@aol.com
Date: 9 Sep 1998 04:08:00 GMT
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I'm taking a molecular biology class.  The professor gave us a problem set.  He
said we could ask anyone for help.  I'm asking you!  Here's the problem:
You want to determine the 3-D structure of a 25 base pair oligonucleotide
duplex.  The sequence is:
5'TTTTTAAAAATTTTTGGGGGGGGGG3'
3'AAAAATTTTTAAAAACCCCCCCCCC5'

A.  Describe the kinds of secondary and tertiary DNA structues that youmight
expect to find in the DNA.
B.  Propose a multi-approach experimental strategy for testing your hypotheses.
 Describe the kinds of information each approach would provide, andhow the
approach could be used to confirm or discount your hypotheses.  What could be
the alternative outcomes and conclusions?

I was considering making a flow chart of the approaches and possible outcomes. 
We've been talking about the various microscopies, NMR and crystallography. 
I'm assuming we would use those methodologies.  

Thanks.


From owner-molec-model@net.bio.net Tue Sep 08 23:00:00 1998
Path: biosci!agate!newsfeed.berkeley.edu!newsfeed.wli.net!uunet!uunet!in1.uu.net!news7-gui.server.ntli.net!news-feed.ntli.net!not-for-mail
From: "David Hemmings" <David.Hemmings@virgin.net>
Newsgroups: bionet.molec-model
Subject: Re: 3-D structure of DNA
Date: 9 Sep 1998 23:32:12 GMT
Organization: Virgin Net Usenet Service       
Lines: 76
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Well you should really show that you have thought about the problem,
before just blindly asking for someone to come up with the solution. 
Just asking will not help you in the long term.
Get a good biochemistry book (Stryer, Voet, Matthews etc.) and a
molecular biology book (Freifelder etc.)

You have a palindromic sequence, AT rich region (multiple 2 Hbonds) GC
rich region (multiple 3 Hbond region)

Think about :

Random Coil
Hbonding (interstrand - obviously) thermodynamically what would GC rich
region confer ?
measure denaturing temp.
 intrastrand H-bonding
HPhobic interactions   (BASE STACKING - nice flat organic molecules
with water about them, what will they do ? Cluster -> Helix
disrupt Hphobic with methanol, TFA, NaCl measure denaturing temp.
measure base stackin (CD, ORD)
Cooperative base stacking
VdW attractions)
amount of 'fraying' at the ends (lack of Hbonding) - what sequenses
give more/less ?
DNA 'brething' (mportant) - what sequences most likely give it ?
motifs -hairpin turns / stem and loop


For 25 base pairs i think microscopies really out, only used on V.large
sections of DNA - giving a gross structure (strand)

NMR - TOCSY, NOESY, INADEQUATE

The higher the % of helix, the stronger pattern seen with X-ray
diffract.


These are just some thoughts, you really should read up on this in the
library.

HTH
DH


Paralee PK <paraleepk@aol.com> wrote in article
<1998090904080000.AAA18636@ladder01.news.aol.com>...
> I'm taking a molecular biology class.  The professor gave us a
problem set.  He
> said we could ask anyone for help.  I'm asking you!  Here's the
problem:
> You want to determine the 3-D structure of a 25 base pair
oligonucleotide
> duplex.  The sequence is:
> 5'TTTTTAAAAATTTTTGGGGGGGGGG3'
> 3'AAAAATTTTTAAAAACCCCCCCCCC5'
> 
> A.  Describe the kinds of secondary and tertiary DNA structues that
youmight
> expect to find in the DNA.
> B.  Propose a multi-approach experimental strategy for testing your
hypotheses.
>  Describe the kinds of information each approach would provide,
andhow the
> approach could be used to confirm or discount your hypotheses.  What
could be
> the alternative outcomes and conclusions?
> 
> I was considering making a flow chart of the approaches and possible
outcomes. 
> We've been talking about the various microscopies, NMR and
crystallography. 
> I'm assuming we would use those methodologies.  
> 
> Thanks.
> 
> 

From owner-molec-model@net.bio.net Tue Sep 08 23:00:00 1998
Path: biosci!news.stanford.edu!Cabal.CESspool!bofh.vszbr.cz!newsgate.cistron.nl!het.net!news.belnet.be!inf6serv.rug.ac.be!not-for-mail
From: Wijnand Schepens <Wijnand.Schepens@rug.ac.be>
Newsgroups: bionet.molec-model,bionet.biophysics,comp.programming,bionet.molbio.proteins,comp.graphics.visualization
Subject: visualizing cluster of simple molecules
Date: Wed, 09 Sep 1998 16:35:06 +0200
Organization: RUG
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Xref: biosci bionet.molec-model:2233 bionet.biophysics:4375 bionet.molbio.proteins:13269

Hi,

I would like to visualize a cluster (set) of small (identical)
molecules.
I now the coordinates of every atom in every molecule. What I'm looking
for is a simple way to see on the screen how it looks like.
- Is there any freeware or shareware program (Windows or UNIX) that does
this
- What file-formats are appropriate for this goal and simple enough?

I've tried to put the coordinates in a pdb-like format, and used rasmol
to visualize it, but they expect proteins, and I don't need all that
fancy stuff...

Can anyone help me along?

Wijnand Schepens




From owner-molec-model@net.bio.net Wed Sep 09 23:00:00 1998
Path: biosci!news.stanford.edu!su-news-feed2.bbnplanet.com!su-news-hub1.bbnplanet.com!news.bbnplanet.com!newsfeed.wli.net!portc04.blue.aol.com!audrey03.news.aol.com!not-for-mail
From: paraleepk@aol.com (Paralee PK)
Newsgroups: bionet.molec-model
Subject: Re: 3-D structure of DNA
Lines: 19
Message-ID: <1998091012044700.IAA07713@ladder03.news.aol.com>
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References: <01bddbfe$495dc4a0$LocalHost@dave>

Yes, you are right.  I need to work out all the possible structures and then
develop an approach to select the correct one.  I'm sorry I didn't proffer any
ideas earlier.  I was just trying to get it out there and get a response--
didn't know how long it would take to get help.-- while I was working on it
myself.  Yes, we are supposed to research it out in the lit and texts.

Why do you think NMR/2-DNOE is inadequate?  I've had another response that NMR
should do it all.  My teacher seems to lead us to 2-D NOE.

I was going to work out the possible structures, then use a selective enzyme
for single stranded DNA to confirm that there were loops running a gel to see
if it was broken and if so into how many pieces to narrow down the options
before moving to the next thing.

Thanks for your help.  May I continue to ask you questions as I work through
this?

Paralee


From owner-molec-model@net.bio.net Thu Sep 10 23:00:00 1998
Path: biosci!agate!newsfeed.berkeley.edu!sunqbc.risq.qc.ca!news-peer.gip.net!news.gsl.net!gip.net!portc01.blue.aol.com!audrey01.news.aol.com!not-for-mail
From: paraleepk@aol.com (Paralee PK)
Newsgroups: bionet.molec-model
Subject: Re: 3-D structure of DNA
Lines: 35
Message-ID: <1998091100394100.UAA26697@ladder01.news.aol.com>
NNTP-Posting-Host: ladder01.news.aol.com
X-Admin: news@aol.com
Date: 11 Sep 1998 00:39:41 GMT
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References: <1998091012044700.IAA07713@ladder03.news.aol.com>

I did kind of wonder about INADEQUATE.  Thanks for clearing that up.  Alot of
the methods you suggest are not in the general texts.  We have been referred to
Glasel's - Introduction to Biophysical Methods . . .  but it isn't available at
the moment (I'm bugging the prof to get it on reserve).

Thank you for your advice.  I did some reading today.  Your clues provided me
with some direction.  I think I'll have some hypotheses by tommorow as far as
the specific probable structures.  Right now I'm pretty sure it:
-isn't circular: need to have 80 bp minimum to circularize
-isn't Z-DNA in any portion: need alternatine purine pyrimidine and
supercoiling that can only occur in circular DNA
-could be 3x helical, but that requires supercoiling/circularization which I'm
assuming we don't have . . . the "breathing and fraying" of the A*T region
wouldn't provide enough energy to make this happen would it?
-could be bent 8.7 degrees for each dinucleotide, best seen if a long repeating
strip were synthesized
-could be slipping- my teacher said left slipping (because of backbone config.)
is preffered, does that mean the 5' end slips to the left/
-is not forming cruciform: supercoiling required for energy needed, hairpin has
to have 3-4 unpaired bases in it, 10 base pairs minimum are required

Do these conclusions seem right? I based them mostly on what I read in Sinden's
book-DNA Structure and Function.

I'm tending to think of using:
NMR-NOE
Tm-Absorbance

At first I wanted to use an enzymatic digest to select for single stranded DNA,
but I don't think there is going to be much.  I need to find out more about
NMR-NOE.  Glasel's book seems to be unavailable here.  Any other resources?

Thank you for your listening ear!

Paralee

From owner-molec-model@net.bio.net Thu Sep 10 23:00:00 1998
Path: biosci!biosci!not-for-mail
From: "clive delmonte" <clived@ndirect.co.uk>
Newsgroups: bionet.biophysics,bionet.molec-model,bionet.xtallography
Subject: Triple-stranded DNA Structure
Date: 11 Sep 1998 08:36:41 -0700
Organization: BIOSCI International Newsgroups for Molecular Biology
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Xref: biosci bionet.biophysics:4389 bionet.molec-model:2240 bionet.xtallography:4392

The formation and properties of triple-stranded DNA are now described in a
substantial body of literature.  However, I have been searching for early
research reports identifying triple-stranded DNA and I have come upon a
problem.   I  would be grateful to hear what thoughts others have had about
it.

Leslie et al.(J Mol Biol 143 (1980) 49-72) reported that a fibre of
poly(dI).poly(dC) which gave sharp X-ray diffraction spots shortly after
being drawn was unstable and transformed irreversibly after a few days into
poly(dC).poly(dI).poly(dC+).  This new molecule also gave sharp spots in its
X-ray diffraction pattern, and this new pattern did not have any of the
original spots.  Therefore the conversion was complete, or substantially
complete.

Very similar results were reported for fibres of poly(dA).poly(dT)
converting to poly(dT).poly(dA).poly(dT) (J Mol Biol 88 (1974) 509-521) and
for the formation of poly(U).poly(A).poly(U) (Nature New Biology 244 (1973)
99-101).

The problem is evident:  How and where would the torque arise inside a solid
fibre that would permit one double helix to rotate so as to unwind one
strand and rewind it onto an adjacent triple helix having a different
diameter and rotating at a different angular velocity ?  Inside the fibre,
individual molecules would have a random axial translation so only very
rarely would two adjacent double helices have the same axial starting point.
How would there be a very high conversion of double to triple stranded
molecules when any rotation of adjacent double helices would normally find
the free ends of one of them axially displaced down the fibre compared to
its neighbour ?

None of the original workers offered any explanation as to how this
conversion might be possible, nor, indeed, remarked that there might be
something to explain.

Naturally I have given this problem some thought, but I have been driven
towards a daunting conclusion.   I shall be glad to share my thoughts with
anyone who lets me know they are interested, or anyone who offers their
thoughts on this problem.

clived@ndirect.co.uk




From owner-molec-model@net.bio.net Thu Sep 10 23:00:00 1998
Path: biosci!agate!newsfeed.berkeley.edu!news.maxwell.syr.edu!rill.news.pipex.net!pipex!server1.netnews.ja.net!hgmp.mrc.ac.uk!csansom
From: csansom@hgmp.mrc.ac.uk (Dr C Sansom)
Newsgroups: bionet.molec-model
Subject: Virtual Reality in drug design
Date: 11 Sep 1998 11:43:14 GMT
Organization: UK HGMP Resource Centre
Lines: 45
Message-ID: <6tb2ci$9ha$1@niobium.hgmp.mrc.ac.uk>
NNTP-Posting-Host: iron.hgmp.mrc.ac.uk

Hello,

Firstly, I would like to thank everyone who replied to my post about
articles for Nature Biotechnology.  The first article, on molecular
modelling, provisionally titled "Extending the boundaries of molecular
modeling", should be published in the October issue.  I'll get back to
those people who specifically wanted to talk about bioinformatics when I
know when the editors will be needing that article. 

That is not all, tho': I have another request.  I edit a regular feature
in "The Biochemist" (the magazine of the UK's Biochemical Society, which
goes out free to all 8000-odd members).  This is called "The Cyber-
biochemist": each article features a new or interesting development in
computing which we hope will interest non-specialist biochemists. I may
either write or commission articles. 

I am intending to feature the uses of Virtual Reality in drug discovery
(current or potential) for the next issue, which has a deadline of the end
of this month. I would be very interested in any potential contributions. 
I would be happy to talk by phone, but you may prefer just to send me your
thoughts, sample Web pages or reviews by email.  Alternatively - if anyone
would like to *write* a short piece on this subject for the Biochemist,
it's not too late.... 

The "rules" of the Cyberbiochemist are very simple.  There is a fairly
strict word limit of up to 700-800 words (not including space for
references, urls and/or one diagram). Articles are to be written in an
informal style and aimed at non-specialists.  As this article will appear
in the Christmas issue, the style will be even more informal than usual ;)

Thank you very much for offers of help, in any format ;)  I must apologise
for the short notice.

Please reply by email, preferably to the address below.


Best regards,

Dr Clare Sansom
c.sansom@mail.cryst.bbk.ac.uk
Honorary Teaching Fellow, Birkbeck College, London, UK
Freelance consultant and science writer




From owner-molec-model@net.bio.net Thu Sep 10 23:00:00 1998
Path: biosci!agate!newsfeed.berkeley.edu!oleane!jussieu.fr!moka.ccr.jussieu.fr!not-for-mail
From: ptitjean@ccr.jussieu.fr (Michel PETITJEAN)
Newsgroups: bionet.molec-model
Subject: sequence alignment poorer than 3D alignment
Date: 11 Sep 1998 12:02:31 +0200
Organization: CCR - Universites Paris VI/VII - Paris - France
Lines: 6
Message-ID: <6tasfn$3sf4@moka.ccr.jussieu.fr>
NNTP-Posting-Host: moka.ccr.jussieu.fr
Mime-Version: 1.0
Content-Type: text/plain; charset=iso-8859-1
Content-Transfer-Encoding: 8bit

Is there some pair of proteins having a sequence homology (% similarity)
significantly lower than their % 3D-similarity ? (any definition of
these percentages should work). References are welcome. Thanks.

Michel Petitjean,                     Email: petitjean@itodys.jussieu.fr
ITODYS (CNRS, ESA 7086)                      ptitjean@ccr.jussieu.fr

From owner-molec-model@net.bio.net Sat Sep 12 23:00:00 1998
Path: biosci!pravda.ucr.edu!awabi.library.ucla.edu!128.230.129.106!news.maxwell.syr.edu!nntp.news.xara.net!xara.net!server5.netnews.ja.net!HEAnet!web3.tcd.ie!acer.gen.tcd.ie!tpwalsh
From: tpwalsh@acer.gen.tcd.ie (Thomas Walsh)
Newsgroups: bionet.molec-model,bionet.biophysics,comp.programming,bionet.molbio.proteins,comp.graphics.visualization
Subject: Re: visualizing cluster of simple molecules
Date: 9 Sep 1998 17:28:42 GMT
Organization: Urmhumhan
Lines: 13
Message-ID: <6t6dsa$1pg@web3.tcd.ie>
References: <35F69219.6C4B8549@rug.ac.be>
NNTP-Posting-Host: acer.gen.tcd.ie
Xref: biosci bionet.molec-model:2245 bionet.biophysics:4393 bionet.molbio.proteins:13292

Wijnand Schepens wrote:
>I would like to visualize a cluster (set) of small (identical)
>molecules.
>I now the coordinates of every atom in every molecule. What I'm looking
>for is a simple way to see on the screen how it looks like.
>
>Can anyone help me along?

 I haven't used it but PREPI might do what you want:

 http://bonsai.lif.icnet.uk/people/suhail/prepi.html

   Tom Walsh

From owner-molec-model@net.bio.net Sun Sep 13 23:00:00 1998
Path: biosci!biosci!not-for-mail
From: "clive delmonte" <clived@ndirect.co.uk>
Newsgroups: bionet.biophysics,bionet.molec-model,bionet.xtallography
Subject: DNA Structure Discussion Continued
Date: 14 Sep 1998 10:56:30 -0700
Organization: BIOSCI International Newsgroups for Molecular Biology
Lines: 1007
Sender: daemon@net.bio.net
Distribution: world
Message-ID: <35fd48d9.0@news.netdirect.net.uk>
NNTP-Posting-Host: net.bio.net
Xref: biosci bionet.biophysics:4396 bionet.molec-model:2249 bionet.xtallography:4399

Bill further asks whether the side-by-side structure set out in my first
attachment does not contradict the structures derived from the fibres.  This
is a key question and requires a full answer (if you'll indulge me a
little.)  There are several aspects to this.  First, Crick had never seen
any of Franklin's (high quality) DNA fibre diffraction patterns when he and
Watson proposed their structure.  Watson had seen a B-DNA pattern only very
briefly and could not study it at leisure.  Plectonaemic winding in DNA had
already been proposed by Pauling & Corey early in 1953 and Watson & Crick
seem to have adopted that idea.

A R Stokes, a colleague and co-worker of Crick, had deduced an important
geometric ratio for the classical helical cross (Prog. Biophys. & Biophys.
Chem. 5 (1955) 140-167, page 163) (see attachment) such that, for the angle
from the vertical (delta), tan delta = helical pitch / (helical
circumference).  In Franklin's famous B-DNA diffraction pattern (see
attachment), delta = 40 degrees approximately, and, as the pitch is known to
be 33.4 Angstroms from the layer lines, we deduce that the major diffractors
lie on a helix of diameter of about 12 to 13 Angstroms.  This is close to
Franklin's deduction of a diameter of 11 Angstroms from her Pattersons.

I now have seventeen published DNA fibre diffraction studies in which the
researchers make it explicitly clear that they chose a unit cell which would
be large enough to accommodate a double helical diameter of some 19-23
Angstroms even though their patterns of systematic absences in the
reflections would have allowed them to choose a smaller unit cell (into
which the double helix could not be fitted.)  I also have references to
unpublished studies in 3 or 4 PhD theses where a larger unit cell was chosen
than the raw diffraction data actually required.  I should be very glad to
forward the list of references to anyone interested.

If you choose the smaller unit cell allowed by the dffraction pattern and
recalculate the helical diameter (a simple geometric exercise, of course),
you get diameters in the range 11.2 to 13.6 Angstroms.

A really fascinating study in conventional chemistry is that of James &
Mazia (Biochim.Biophys.Acta 10 (1953) 367-370).  They discovered that 1 mg
of dry calf thymus DNA could be spread in a monolayer to cover 0.28 square
metres.  They didn't notice that from just this result alone we can directly
estimate the minor axis diameter of the duplex as 11.7 Angstroms.  I would
be very glad if people would like to calculate the diameter for themselves
and compare their sums with mine.  (James & Mazia measured the major axis
diameter, that is the height of the spread film in a separate experiment as
21.6 Angstroms.  Therefore their results lead us to a duplex with an
elliptical section.)

The new model for DNA structure leads to the presence of a "front" and a
"rear" face with great implications for protein-DNA recognition, including
the way such DNA would wind onto nucleosomal cores, for example.

What problems would people see with this account so far, please ?
Perhaps from NMR or diffraction from true crystals of oligonucleotides ?
clive delmonte
clived@ndirect.co.uk




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end


From owner-molec-model@net.bio.net Sun Sep 13 23:00:00 1998
Path: biosci!biosci!not-for-mail
From: "clive delmonte" <clived@ndirect.co.uk>
Newsgroups: bionet.biophysics,bionet.molec-model,bionet.xtallography
Subject: The Structure of Duplex DNA
Date: 14 Sep 1998 10:54:57 -0700
Organization: BIOSCI International Newsgroups for Molecular Biology
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Xref: biosci bionet.biophysics:4395 bionet.molec-model:2248 bionet.xtallography:4398

Eric,

You are right, and it is timely, to raise the topological papers by Crick,
Wang & Bauer (J Mol Biol 129 (1979) 449-461), and Bauer, Crick & White
(Scientific American 243 (1980) 100-113).  Their treatments did not apply to
every side-by-side model, however :

"..This proves that the linking number is not equal to zero (at least for
the great majority of those, i.e., side-by-side, molecules.),

and also only to such side-by-side models

"...in which the two ...chains do not coil around each other ...but instead
lie side by side over most of their length, having only a few helical
turns."

Their treatment only applies to side-by-side models, like that of Rodley et
al., for which there is a net winding because an equal number of right and
left turns do not get you back to an equivalent repeat point in space
because of the D chirality of asymmetric carbon in all the pentoses.

The model I have come upon has exactly and identically zero plectonaemic
turns in its relaxed state over any length of duplex and is therefore not
covered and constrained by the two papers just cited.

Thermodynamics has always been a delight to me, though I find it difficult!
Chemical energy is dissipated in all directions; that is, it is not a
vector, but torque is a vector.  Therefore chemical energy would seem to be
unable to either wind or unwind two plectonaemic strands where no breakage
of covalent bonds takes place.  My solution to this conundrum is to say that
neither winding nor unwinding does actually take place !

But tell me - let me tease you a little - what do you make of the results of
Kabata et al. (SCIENCE 262 (1993) 1561-1563) who found that RNA polymerase
slides along its DNA duplex substrate and does not follow a helical path ?

An absolutely crucial test of the new model offers itself, though we need
someone to carry it out.  Drew & Travers (J Mol Biol 186 (1985) 773-790)
have constructed a 169 bp circular, covalently closed length of duplex DNA.
With this length of DNA there can only be a very limited number of
topoisomers present if the ring closure, of itself, could introduce only a
very few superhelical turns.  That is, all the 169 bp molecules would share
a range of superhelical turns between about -1 and +1.  Therefore in
suitably mild denaturing conditions, in the absence of any strand breakage,
the 169 bp sequence would be largely separable into complementary covalently
closed single-stranded DNA circles interlinked at very few places according
to the new model. Thus the most direct route to distinguishing between the
DNA double helix and the new model is based on topology.  The complementary
strands in that 169 bp sequence may actually be linked by 0, or perhaps ± 1
superhelical turns due to the algebra of the enzymic closure reaction used
on the 169 bp linear duplex, and the denatured covalently closed circular
strands could be decorated with a suitable protein and then be examined
under AFM to determine their linking number.

Therefore, if the 169 bp circular DNA is denatured under mild conditions,
perhaps using aqueous urea, it could then be decorated with the
single-strand DNA binding protein, the product of gene 32 from phage T4
(Scanning Microscopy 9 (1995) 705-727), so as to be rendered easily visible
under AFM, and the actual numbers of crossovers then counted.

According to the double helix model, LK will lie in the range 16 to 18, or
so, while the new model predicts LK is -1, 0 or +1.

A very similar experiment could be carried out with the small circular DNAs
described by Bates & Maxwell (EMBO J 8 (1989) 1861-1866), where, for the
smallest, the double helix model predicts LK = 9, and the new model predicts
LK = -2.

Is there any research group with the interest and ability to conduct this
experiment ?


clive delmonte
clived@ndirect.co.uk


From owner-molec-model@net.bio.net Sun Sep 13 23:00:00 1998
From: "clive delmonte" <clived@ndirect.co.uk>
Newsgroups: bionet.biophysics,bionet.molec-model,bionet.xtallography
Subject: Triple-stranded DNA Discussion on Structure
Date: Mon, 14 Sep 1998 14:56:16 +0100
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Xref: biosci bionet.biophysics:4394 bionet.molec-model:2247 bionet.xtallography:4397

Let me thank Eric Fairfield, Kandala Chary and Bill Ross for their helpful,
initial comments made in response to my request on 11th September for
suggestions as to how the problem of triple strand formation inside fibres
might be resolved.

Kandala suggests that:

"In poly(dI).poly(dC) and poly(dA).poly(dT) sequences dI and dA strands have
a propencity to accept the third strand on the major groove side. And in
poly(dI).poly(dC) and poly(dA).poly(dT) mixtures, before they are drawn into
fibres, the duplexes are in dynamic equilibrium with monomeric strands.
Thus, when one forms fibers, the need to unwind a duplex is not necessary.
There are sufficient monomeric strands which hug to the duplexes, thus
forming stable irreversible triplexes. I hope this will answer your
question."

These are very interesting points but it seems to me that there may be some
difficulties with them.  The dynamic equilibrium existing between single
strands and duplexes could be seen to invite a very similar point about how
exactly a duplex unwinds in solution during denaturation.  Where does the
torque come from ?  I have never seen this question addressed.

The unwinding situation in solution is very similar in biophysical terms to
that found in fibres during triple strand formation when one duplex also has
to "unwind", it seems to me.  Moreover, in solution, the duplex is folded
into 3 dimensions, compared to being linear in fibres, and unwinding might
be even harder than in fibres.

As I recall, the major groove does not exist on one side of a duplex, but
follows a helical path around the duplex axis. If a third strand is to join
the first two by lying in the major groove, it would have to be wound onto
the original duplex, I believe.   The initial fibre X-ray diffraction
patterns were characteristic of those ascribed to duplexes and distinct from
single strand diffraction patterns (from poly(rC) and from poly(rA), for
example).  Therefore single strands would seem to have been absent
initially, but were produced in forming the triplex plus a residual single
strand over a period of some days after the young fibre had been drawn.

Bill suggests that:

"Not knowing much about fiber diffraction, it's easy enough to speculate
that somehow the original duplex was somehow not really a duplex, but
assuming it was, I wonder if you are thinking about bond breaking, maybe
some sort of autocatalytic mechanism."

Again, I am grateful for these very interesting suggestions.  Even if the
initial duplexes were not really duplexes, they would seem to have wound
around each other to form the final triplex (assuming that winding around
was involved in triplex formation !)   I think that here lies actually the
germ of the answer.  The initial duplexes were not duplexes in the sense
that the strands were wound around each other, and the final triplex
structures did not involve any strands winding around each other either.
There was no unwinding and no winding either.

This would then become the explanation of denaturation.  The duplexes are
not composed of two strands wound around each other, but two helical strands
running antiparallel alongside each other.  During denaturation the two
helical strands could then move apart in a linear direction.  In triplex
formation in a fibre, one strand moves in a linear manner from its initial
partner to an adjacent duplex. Probably the helical sugar-phosphate chains
would move hardly at all, but the bases might rotate to reach their new
partners.

I wonder if you recall the paper by Kabata et al. (SCIENCE 262 (1993)
1561-1563) ?  They found that single molecules of RNA polymerase were
sliding along tethered molecules of duplex DNA.  The polymerase did not
describe a helical locus at all.  The DNA was immobilised and could not
rotate and nor did the polymerase rotate either.   If duplex DNA consisted
of two chains wound around each other, how would the polymerase "read" the
message on the alternate half turns of the duplex which lay on the other
side away from the polymerase ?  Would that not require two reading
mechanisms, one each to be used on alternating half turns ?  This would
hardly be conducive to high quality transduction of the message contained in
the base sequence.  Kabata et al. did not address this question.   If the
DNA actually consisted of two antiparallel helical chains running alongside
each other, the RNA polymerase could remain on the same face of the duplex
and read the whole message.

Attached to this note should be a diagram of the structure of duplex B-DNA,
if I understand the scanner software, which I believe can account for all
the experimental results with DNA which are known to me and would be very
glad to consider with you what you think its limitations might be. Each
sugar-phosphate helix would have the same diameter as the width of a
Watson-Crick base pair, about 11 Angstroms, and the same pitch as a
Watson-Crick B form double helix, about 34 Angstroms.

 Aaron Klug told Robert Olby in "The Path to the Double Helix", page 373,
that Rosalind Franklin had been working with her Pattersons on separate
helices of diameter 11 Angstroms, which would have been before she could
have known about Watson-Crick base pairs (whose width is necessarily close
to 11 also in order to make the geometry work).


You may know Max Delbruck (Watson's tutor) wrote to Watson in 1953:

 "These (DNA strands) would have to be untwiddled to separate the
threads....In any event, one must postulate that the DNA opens up in some
manner, both for replication and for doing its business otherwise.  In the
structure you describe this opening up is opposed both by the two hydrogen
bonds per nucleotide, and by the interlocking
 of the helices, and it becomes a very important consideration to find a way
out of this dilemma, or to think of a modification of the structure that
does not involve interlocking."

Delbrück's prescience stands out across 40 years and more.

I have been actively scouring the X-ray and NMR literature to bring together
those many experimental results which would seem to support the suggested
side-by-side model.  If you would wish to follow the experimental results
further along what I find a very absorbing avenue of thought do let me know.



begin 666 Views of B DNA take 2.xif
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