From owner-biophysics@net.bio.net Tue Feb 02 22:00:00 1999 From: "Clive Delmonte" Newsgroups: bionet.biophysics,bionet.xtallography Subject: DNA Structure: An Age of Refinement Part 5 of 6 Date: Wed, 3 Feb 1999 09:51:49 -0000 Lines: 112 X-Newsreader: Microsoft Outlook Express 4.72.3110.5 X-MimeOLE: Produced By Microsoft MimeOLE V4.72.3110.3 NNTP-Posting-Host: 195.7.225.6 Message-ID: <36b81714.0@news.netdirect.net.uk> X-Trace: 3 Feb 1999 09:29:56 GMT, 195.7.225.6 Path: biosci!agate!newsfeed.berkeley.edu!diablo.theplanet.net!news.freedom2surf.net!peer.news.nildram.co.uk!news-peer.netdirect.net.uk!news.netdirect.net.uk!195.7.225.6 Xref: biosci bionet.biophysics:4752 bionet.xtallography:4577 Definitions and Nomenclature of Parameters used to define Nucleic Acid Structures In 1989, a group of some sixteen prominent crystallographers, drawn from many of the best-known research groups with an interest in oligonucleotide structural studies, met in Cambridge to seek "...the creation of...routines for the analysis and description of polynucleotide structure, especially, but not exclusively the DNA double helix." (79,80,81) In Figure 2 (79, page 788) are defined the "...local reference axes (x,y,z) at the first two base pairs of an n base-pair double helix." On page 789 we read "With these conventions, the signs of helical twist Omega, propeller twist omega, displacement dx, and inclination eta, for three families of DNA double helix typically are as follows:..." The decisions taken in Cambridge certainly influenced some researchers at least (82, page 657): "The choice adopted in Cambridge concerning the axis system describing the double helix leads us to modify the base fixed axis system (of CURVES) which serves to locate any given nucleotide in space." Understood literally, it seems evident that the conference participants in Cambridge undertook to conduct future crystallographic studies of oligonucleotides, at least, as they had perhaps been doing already anyway, in such a way that there could be only one possible allowed structural outcome, namely, the double helix. It would not matter whether heavy atoms were used, or MAD, or synchrotron sources, or the use of allegedly ab inititio methods, or whatever; since only one structural outcome would be possible. Many algorithms have been used to determine oligonucleotide structure, such as, CORELS, DBLHLX, HELIX, NEWHELIX, NUCLSQ, SHELX93 and ULTIMA, for example. Doubtless it would be unfair merely to assume that all these programs, or the context of their use, incorporated directly or indirectly, explicitly or implicitly, an a priori acceptance of the DNA double helix, but, unfortunately, explicit details of the working of the algorithms, and the context of their use, do not seem to be widely and publicly available. The experimental, published results identified in the Puzzles, and more extensively elsewhere (42,64), pose a severe and so far unanswered test of the double-helical paradigm. It would seem appropriate therefore, in view of the Cambridge meeting (79 - 81) which appears to limit crystallographic outcomes solely to one duplex model, and because of the continuing great importance of work with duplex DNA in many fields of biochemistry, biophysics and molecular biology, for researchers in these fields to consider asking their professional societies to reflect upon the merits of recommending a moratorium on all future citations of the work and results of studies in oligonucleotide crystallography until certain, satisfactory clarifications have been forthcoming in the literature. These could include statements, supported by publication of the algorithms in an accessible format, defining: a) the precise philosophy underpinning the program and any relationship it may have to the double helical paradigm, b) the precise structural origin of any library data used by the program, c) the precise character and purpose of any manual intervention by the investigators themselves during refinement, d) the precise origin of any data on models used in a study to help determine the structure of a new oligonucleotide, and e) the ready availability of all the structure factor files, many of which are not accessible via the Brookhaven National Protein Data Bank (PDB). Until these conditions have been fully met, and the problem of the many outstanding unexplained results reported in the literature, and reviewed elsewhere (42, 64), has been fully addressed, the professional societies may elect to consider that the oligonucleotide structures held at PDB and elsewhere are insecure. The current situation reflects that described by Francis Bacon in 1620: "The human intellect, in those things which have once pleased it...brings everything else to support and agree with it; and though the weight and number of contradictory instances be superior, still either overlooks, or despises, or gets rid of them...that the authority of these previous conclusions may remain inviolate." -------------------------------------------------------------- 79 Definitions and Nomenclature of Nucleic Acid Structure Parameters; R.E. Dickerson et al.; J Mol Biol Vol 205 (1989) 787 - 791 80 Definitions and nomenclature of nucleic acid structure components; R.E. Dickerson et al.; Nucleic Acids Res Vol 17 (1989) 1797 - 1803 81 Definitions and Nomenclature of Nucleic Acid Structure Parameters; Reported by R.E. Dickerson; J Biomol Struct & Dyn Vol 6 (1989) 627 - 634 82 Defining the Structure of Irregular Nucleic Acids: Conventions and Principles; R. Lavery & H. Sklenar; J Biomol Struct & Dyn Vol 6 (1989) 655 - 667 -------------------------------------------------------------- Clive Delmonte .