From owner-biophysics@net.bio.net Wed Feb 10 22:00:00 1999 Message-ID: <36C249C8.BAF3AED2@bioreason.com> Date: Wed, 10 Feb 1999 19:08:56 -0800 From: Andrew Dalke Organization: Bioreason, Inc. X-Mailer: Mozilla 4.05 [en] (X11; U; IRIX 6.2 IP22) MIME-Version: 1.0 Newsgroups: bionet.biophysics,bionet.xtallography Subject: Re: Is ignorant rambling, was: DNA Structure: An Age of Refinement... References: <36b81714.0@news.netdirect.net.uk> <36BE3682.977F323B@bioreason.com> <36beffa3.0@news.netdirect.net.uk> <36BF48D4.B38DC74E@bioreason.com> <36c1be39.0@news.netdirect.net.uk> Content-Type: text/plain; charset=us-ascii Content-Transfer-Encoding: 7bit NNTP-Posting-Host: dialup2.trail.com Lines: 53 Path: biosci!agate!newsfeed.berkeley.edu!news-peer1.sprintlink.net!news.sprintlink.net!nntp.abs.net!outfeed1.news.cais.net!news4.his.com!dialup2.trail.com Xref: biosci bionet.biophysics:4776 bionet.xtallography:4595 "Clive Delmonte" said: > You mention that the force field calculations give reasonable energies > for the double helix and that the conformation should be expected quite > often, but I find myself wondering what that means. The double helical > conformation should be expected quite often compared to what > alternatives ? Energetically speaking, if an unknown but more common conformation exists, then from a Bolzmann distribution, the binding energy must be at least somewhat higher than that of a double helix. (The ratio of the number of states in two different energy states at equilibrium is = exp(- delta E / kT) .) The estimate of the binding energy from the free state to the bound state is known experimentally and is comparable to that predicted by MD (though there is still a rather large error range and I don't know a reference comparing them; with all those charges it's a hard computation). Thus we have three pairs of energy differences: free -> double strand double strand -> conformation X (that required for your proposal) free -> X Let's assume the numbers from http://mills.edu/RESEARCH/FUTURES/JOHNB/structurefunction/708.html are correct (they are the first I found): A-T binding is 10 kJ/mol G-C binding is 15 kJ/mol For conformation X to exist over 95% of the time requires 0.05 = exp(-E/2.494) delta E = E(double strand) - E(conformation X) is about 7 kJ/mol (assuming I got kT right for kilojoules at 300 Kelvin). That's a big energy difference between them, and given that I don't think the error estimates from molecular force fields calculations have that large an error, I cannot believe there is a conformation that much more energetically favorable than a double stranded model. Thus, I strongly believe you have misinterpreted the data from the articles you referenced. As I have not the time, expertise nor inclination to look them up, I cannot give my own interpretation. Energy arguments suffice for me to stay with the current model until someone shows me a predicted structure with sufficient explanatory power, and you have not done so. Andrew Dalke dalke@acm.org .