From moret ^%at%^ far.ruu.nl Tue Dec 20 17:26:19 1994 Received: from accucx.cc.ruu.nl for moret-!at!-far.ruu.nl by www.ccl.net (8.6.9/930601.1506) id QAA04806; Tue, 20 Dec 1994 16:49:52 -0500 Received: from far.ruu.nl (ruucmc.far.ruu.nl) by accucx.cc.ruu.nl with SMTP id AA20370 (5.65c/IDA-1.4.4 for ); Tue, 20 Dec 1994 22:49:44 +0100 Message-Id: <199412202149.AA20370-: at :-accucx.cc.ruu.nl> Received: by ruucmc.far.ruu.nl (16.6/16.2) id AA14967; Tue, 20 Dec 94 22:47:07 +0100 From: "E.E.Moret" Subject: Summary dendrimer modelling responses To: chemistry /at\ruucmc.far.ruu.nl Date: Tue, 20 Dec 94 22:47:06 MET Name: Ed Moret Organisation: Utrecht University Phone: 030 - 536979 Mailer: Elm [revision: 66.25] Dear colleagues, Here is the summary of responses to my question on growing dendrimers in computro. There seem to be several possibilities. Polygraf was mentioned twice. CavityStuffer seems very promising when you consider the expected boom of nanotechnology. Thanks to all responders for their generous help. With best regards and season's greetings, Ed Moret Date: Thu, 8 Dec 1994 07:10:04 -0600 From: toni-: at :-athe.wustl.edu (Toni Kazic) Subject: Re: CCL:Dendrimer modelling Klotho handles any number of branch points as a matter of routine. We have not described any dendrimers of the type you describe, but would be happy to. We have not yet released the code (we will, we just need to finishing writing it up), but would be happy to supply pdb files within the limits of what can be generated by CONCORD. We can of course provide the equivalent of an enriched connection table. Toni Kazic Institute for Biomedical Computing Washington University Date: Thu, 8 Dec 1994 09:00:22 -0800 (PST) From: wallyr[ AT ]netcom.com (Walter E. Reiher III) Subject: Re: CCL:Dendrimer modelling E.E.Moret wrote: > Dendrimers are branched polymers, resembling trees and branches, of an > organic repeat unit. Several theories on their potential use have been > proposed (for example Jansen et al., Science 18 november 1994, 1226-1229). ... > We would appreciate any suggestions on research performed in this area and > on programs that can cope with this special kind of "molecular growth". > Replies, if any, will be summarised for CCL. I am certainly not current in this area, but learned a bit about it a few years back when I worked for a software company called BioDesign. That company's polymer product, Polygraf, was capable of building, displaying, and simulating dendrimers. It was used in Bill Goddard's research group at Caltech in some publications. I know one graduate student of Bill's who published in this area: Adel Naylor; there are probably others. You might wish to check their publications near the 1989-1990 timeframe. BioDesign has since become a part of Molecular Simulations. I'd be very surprised if that Polygraf functionality wasn't somewhere in their current product offerings. Hope this helps! Wally ======================================================================== Walter E. Reiher III, Ph.D. WallyR- at -netcom.com Consultant in Computational Chemistry P.O. Box 61056 voice 408-720-0240 Sunnyvale, CA 94088 fax 408-720-0378 Date: Thu, 8 Dec 94 11:23:06 -0300 From: g112976#* at *#iris.ufscar.br (Augusto C. C. Neto) Subject: First Contact Federal University of Sao Carlos, december 7, 1994 Dear Dr Moret We are a experimental&theorical group developing ceramic and semiconductors materials in Brazil . Nowadays I am working with Starburst dendrimers too, I'm using Hyperchem for SGI and Windows, MOPAC 5.0 and Gaussian to calculate my molecules. We are working with Carbon, Nitrogen and Benzene dendrimers. About constructing the generations, they are handmade. What kind of dendrimers's properties you would like to analise ? Do you have a good computer hardware ? Sincerely Augusto Cesar Date: 08 Dec 1994 14:38:34 -0800 (PST) From: CALEF:~at~:HEVXA.llnl.gov Subject: Dendrimers Two quick points. 1) There a class of materials called aerogels that are made of dendrimers. For example resorcinal and formaldehyde link together with three links to each phenyl ring. 2) I use to have POLYGRAF from Molecular Simulations and it had a dendrimer growing option. The problem in that you started with one seed and grew generations out from it - if you wanted "loops" you had to edit them in by hand. What it created was like a Bethe lattice - and as such sooner or later you got molecular overlap. I used it ot make a few viewgraphs. Dan Calef calef ":at:" hevxa.llnl.gov Date: date\r\e%, 8 Dec 1994 19:05:19 -0800 From: kr /at\shell.portal.com (kr) Subject: Re: CCL:Dendrimer modelling At 03:12 94-12-08, E.E.Moret wrote: >We would like to study the influence of the conformation of >the repeat-unit on the multiple-generation dendrimer that can be constructed. >We are aware of software tools to polymerise repeat-units, especially >the modules implemented in the commercial modelling packages. These >modules, however, require ONE head and ONE tail atom to initiate >polymerisation. >Dendrimers, by definition, grow on 3 or more sites of the repeat unit. > >We would appreciate any suggestions on research performed in this area and >on programs that can cope with this special kind of "molecular growth". Dear Ed Moret Until about one year ago, I have worked on a program that would likely be able to accomplish what you are interested in (since then I essentially had no time to further pursue this project). As the "official" description attached below shows, the program I developed is called "CavityStuffer" and was developed to study the design of folding polymers, which can be tree-like with arbitrary branching patterns, and so starburst dendrimers would be a subclass of the tractable structures. The goal of the program was to construct polymers which are able to densely fill a prescribed volume, to design protein-like building blocks that could be used for self-assembly into larger structures. The full goal has so far not been achieved, and I would have to invest more work. The problem is that the current primitive (random) strategy is not able to adequately fill the empty spaces (or it would take too much time to be really useful). But there is a working framework of code that is able to construct libraries of moieties (molecules that can be added as monomers) and of links (which describe the attachment geometry between moieties). Facilities for I/O using the PDB format exist, and a clash detector is able to determine steric clashes in 3D space. There are facilities to manage the tree-like polymer structures with additional associated infrastructure. This framework could easily be extended to grow polymers of predefined sequence (thereby not using certain sections of the program, which are supposed to figure out suitable sequences by themselves :-). The program is written in Common LISP, because it is a suitable language for dealing with complex, arbitrary, and dynamically changing structures, without the hassles of coding all the memory management stuff by hand. And so it is practical for exploratory research. Of the useful and higher level programming languages, Common LISP also has the advantage that it can be obtained for running it on a wide variety of platforms. There are at least two implementations available in source code that run on UN!X boxes, namely GCL/AKCL and CLISP (the latter one from Germany). I would be willing and interested to cooperate and help in adapting the program to the use for starburst dendrimers and other purposes. The only caveats are the following: some sections of the program are not yet very user-friendly, and could use work on designing better facilities for interaction, to which I did not yet get around to implement. Also, there is little documentation, and I plan to write some both on the overall program structure, as well as documenting individual subroutines. Possibly in a few months from now, this better documentation will exist, and I will then post the program on a ftp site for public downloading and experimentation. Until that time, I would be willing to give a copy of the source code to seriously interested parties, and help them as far as I can find time. The only other caveat is that I am opposed to patents, and especially software patents (contact for more info), and so I would object if any part of the program used in derivative work would become covered by patents. Note that even academic institutions often have aggressive so-called technology transfer programs, which achieve exactly the opposite by oppressing everybody's freedom. If it can be assured that CavityStuffer can be held outside of these greedy hands, I encourage free use and exploration. The following is a description of the CavityStuffer program. Note that it chooses the moieties (monomers) that ought to be attached using a random strategy currently, but obviously this could be easily replaced by a dictated, pre-defined sequence. =========================================================================== CavityStuffer Program Description Context The anticipated development of molecular manufacturing capabilities and of molecular nanotechnology hinges on being able to design and synthesize molecular machinery, which consists of well-defined molecular aggregates of a size which is fairly large by today's synthetic standards (linear dimensions on the order of 100nm). Well thought-out ways of convergent synthesis and convergent self-assembly have to be applied to achieve this goal. The critical ability needed seems to be a routine way of designing and synthesizing polymeric macromolecules of about the size of a medium protein. They can be thought of as cubes with a side length of about 3nm. These sub-units need to have complementary surfaces, specifiable to atomic detail, and their cores have to pack into a rigid and immobile structure so that the surface patterns are upheld in a stable fashion. Description of the Program The purpose of the CavityStuffer program is to propose tree-like polymeric molecules, which when synthesized and allowed to fold into their globular structure, will densely fill a given volume, the surface of which was prescribed to atomic detail. The CavityStuffer currently generates its proposals by growing polymers blindly, choosing in a randomized fashion sites on the tree for further attachment and elongation. Once a site has been chosen, a moiety (monomer) is selected from a library of allowed moieties, similar in concept to allowed moves in a game of chess. The moieties are stored in the library as rigid, three-dimensional puzzle-pieces (as rotamers), so the CavityStuffer program works by trying to fit three-dimensional geometric shapes into the given volume. Whenever a chosen moiety does not fit (i.e. if it clashes with other atoms already in place), it is discarded, and a different moiety will be tried instead. This scheme largely avoids expensive numerical tasks such as energy calculations (which are commonly used for studies of folding polymers such as proteins), because clash-detection is quick. Because the generation of individual proposals is fast, a large number can be generated automatically without human supervision and sorted according to how well they fill the volume. There are various places in the program where one could add in smarter and higher-level strategies than the random selection mechanism used now. Current Status As of November 1993, the basic machinery of the CavityStuffer program is working. One can build tree-like molecules using moieties provided by a library. There are also tools to help with constructing the moiety-library, and there are facilities for input and output via PDB files. The program is written in CommonLISP and consists of about 15 files with about 250 lines each. With a simplistic demo-version of the moiety-library, the packing of the polymer is not yet very good. More work has to go into a careful design of a good moiety-library which contains a high enough diversity of rotamers. Better strategies need to be added as well, such as a pre-partitioning of the total volume into smaller chambers, so that the packing becomes a more local task. Acknowledgement CavityStuffer by M. Krummenacker, with valuable input from K. E. Drexler. The work has been funded through the Institute for Molecular Manufacturing, Palo Alto, CA. People interested in staying up-to-date on the development of this program are welcome to send e-mail to . =========================================================================== To understand more of the background thinking that has led to the tackling of the CavityStuffer project, please read my paper describing design rules for organic molecules to be used as molecular building blocks (Chem. Design Autom. News, Vol.9, Jan '94, p.1). If you have difficulties finding this, I can send you a copy if you supply me with your snail-mail ( v_ \\at// _ ) address. I will be in Switzerland for one month starting from Dec. 14, so it would be best to contact me before then, if you are interested. >Replies, if any, will be summarised for CCL. I would be interested in seeing a summary. I also do not mind if my message here shows up on the summary. Many Greetings ================================================================== Markus Krummenacker 1797 Union Street Director of Research San Francisco, CA 94123 Nanothinc, A California Corporation Phone: (415) 202-9969 direct email: kr |-at-| nanothinc.com FAX: (415) 202-9975 general info: info%!at!%nanothinc.com URL: Coming this fall ------------------------------------------------------------------------- E.E. Moret (;at;more;at;) E.E.Moret;at;far.ruu.nl Computational Medicinal Chemistry/Department of Pharmaceutical Chemistry Faculty of Pharmacy/Utrecht University/the Netherlands Telephone (31-30)536979/536958 Facsimile (31-30)516674 -------------------------------------------------------------------------