From owner-biophysics@net.bio.net Sun Jan 31 22:00:00 1999 From: "Clive Delmonte" Newsgroups: bionet.biophysics,bionet.xtallography Subject: DNA Structure: An Age of Refinement Part 4 of 6 Date: Mon, 1 Feb 1999 09:47:23 -0000 Lines: 91 X-Newsreader: Microsoft Outlook Express 4.72.3110.5 X-MimeOLE: Produced By Microsoft MimeOLE V4.72.3110.3 NNTP-Posting-Host: 195.7.227.231 Message-ID: <36b572f2.0@news.netdirect.net.uk> X-Trace: 1 Feb 1999 09:25:06 GMT, 195.7.227.231 Path: biosci!news.stanford.edu!logbridge.uoregon.edu!news.maxwell.syr.edu!voyager.nildram.com!peer.news.nildram.co.uk!news-peer.netdirect.net.uk!news.netdirect.net.uk!195.7.227.231 Xref: biosci bionet.biophysics:4749 bionet.xtallography:4573 ULTIMA - An Approach by Rabinovich & Shakked (72) ULTIMA is presented as a computer program which, inter alia, can be used in a manner so as to solve the structures of crystallised oligonucleotides ab initio. While this very obviously represents excellent current practice, some detailed scrutiny might be warranted in the light of earlier Parts in this series. First, the process seems to have been influenced by knowledge of the double helix model, whose conformation seems to have informed the distances apart chosen by the researchers for the phosphate, sugar and base components (72, page 197). Partly refined (double helical) structures were the result, an outcome perhaps predetermined by the conformational library. Next, during the refinement process, the partly refined structures from ULTIMA were compared with idealised structures for high polymer DNA published by Arnott & Hukins (73) which are informed by prior knowledge and acceptance of the double helix. Rabinovich & Shakked seem to have selected the ULTIMA structure having the best fit to the Arnott & Hukins model and then refined it further using CORELS (Part 3 of 6). As with many other studies, a further, more general difficulty may relate to the choice of unit cell dimensions, when there is a choice, since the cell dimensions in (72) accord well with those chosen earlier by other workers who knew they had to accommodate the Watson-Crick double helix in their unit cells. The choice of unit cell dimensions, where there is discretion, will determine, of course, the axial scales in Patterson and other maps and may force algorithms to move towards a double-helical diameter to fill the chosen unit cell. The literature contains many examples of x-ray diffraction from true oligonucleotide crystals where the reported patterns of systematic absences, sometimes plus weak presences, would have allowed the original researchers to have chosen a smaller unit cell, for example, 74 (A-DNA), 75 (B-DNA), 76 (B-DNA), 77 (Z-DNA) & 78, into which reduced unit cells a double helix would not fit. Systematic weak presences are supposed to arise from distortions of the (large) unit cell which diminish the intensities otherwise to be expected. However, their very existence could arise from distortions of a small unit cell from whose diffraction patterns they would otherwise not have been observed at all. Crystallographers rarely discuss in detail the patterns of systematic absence plus any systematic weak presences to be seen in their structure factors, and the Brookhaven oligonucleotide structure factor files on deposit often reveal patterns which would seem to warrant further close analysis. For the DNA double helix, such is "the intensity of (our) conviction that (the) hypothesis is true", to use Sir Peter Medawar's phrase, that we may be able to agree with John Stuart Mill: "When has there been a dominion which has not appeared natural to them that possess it?" --------------------------------------------------------------------------- 72 A New Approach to Structure Determination of Large Molecules by Multi-dimensional Search Methods; D. Rabinovich & Z. Shakked; Acta Cryst. Vol A40 (1984) 195 - 200 73 S. Arnott & D. Hukins; Biochem. Biophys. Res. Commun. Vol 47 (1972) 1504 - 1509 74 Molecular Structure of d(GTGTACAC) in the spermine-bound tetragonal and the spermine-free hexagonal crystal forms; Sanjeev Jain, PhD Thesis; University of Wisconsin at Madison (1990) 75 Double helix conformation, groove dimensions & ligand binding potential of a G/C stretch in B-DNA; Udo Heinemann, Claudia Alings & Manju Bansal; The EMBO J Vol 11 (1992) 1931 - 1939 76 Unusual helical packing in crystals of DNA bearing a mutation hot spot; Y Timsit et al.; Nature Vol 341 (1989) 459 - 462 77 A Salt-induced Conformational Change in Crystals of the Synthetic Tetramer d(CGCG); H.R. Drew, R.E. Dickerson & K. Itakura; J Mol Biol Vol 125 (1978) 535 - 543 78 The Crystal & Molecular Structure of a Calcium Salt of Guanylyl-3',5'-Cytidine (GpC); B. Hingerty et al.; Acta Cryst. B32 (1976) 2998 - 3013 ------------------------------------------------------------ Clive Delmonte .