The conformational space of monosaccharides is amazingly complex. If we consider just the pyranose form, the ring can in principal exist as a chair, a half-chair, skew (or twist boat) and boat form, for a total of 38 puckering configurations. Layer on top of this the axial and equatorial positions of the hydroxyl and methylhydroxyl groups, and then the rotamers of these substituents, and one is faced with a dauntingly vast space. It is just this space that Beckham and co-workers1 take on for α- and β-glucose, β-xylose, β-mannose and β-acetylglucosamine.
For each sugar, and for each of the 38 puckering configurations, full rotamer scans for each of the substituents led to 27,702 conformations of each of the four monosaccharides, and 36,936 conformations of β-acetylglucosamine. This totals to over 123,000 geometry optimizations that were carried out at M06-2x/6-31G(d). Then taking the structures within 5 kcal mol-1 of the lowest energy structure for each pucker, they reoptimized at M06-2X/6-31+G(d,p). Pruning once again those structures that were above 5 kcal mol-1 of the minimum, they performed CCSD(T)/6-311+G(d,p)//B3LYP/6-311+G(2df,p) computations. What a tour de force!
The results of these conformational space surveys are not terribly exciting. The substituents do make a difference in dictating the most and least favorable structures and the activation barriers for interconversion of ring forms.
These PESs will be quite useful in understanding carbohydrate conformations and the role these may play in their chemistry. But the point of bringing this paper to your attention is the tremendously complex, detailed PES that is uncovered, representing the scale of what can be done with modern computers and modern algorithms.
References
(1) Mayes, H. B.; Broadbelt, L. J.; Beckham, G. T. "How Sugars Pucker: Electronic Structure Calculations Map the Kinetic Landscape of Five Biologically Paramount Monosaccharides and Their Implications for Enzymatic Catalysis," Journal of the American Chemical Society 2013, 136, 1008-1022, DOI: 10.1021/ja410264d.
InChIs
α-glucose: InChI=1S/C6H12O6/c7-1-2-3(8)4(9)5(10)6(11)12-2/h2-11H,1H2/t2-,3-,4+,5-,6+/m1/s1
InChIKey: WQZGKKKJIJFFOK-DVKNGEFBSA-N
β-glucose: InChI=1S/C6H12O6/c7-1-2-3(8)4(9)5(10)6(11)12-2/h2-11H,1H2/t2-,3-,4+,5-,6-/m1/s1
InChIKey=WQZGKKKJIJFFOK-VFUOTHLCSA-N
β-xylose: InChI=1S/C5H10O5/c6-2-1-10-5(9)4(8)3(2)7/h2-9H,1H2/t2-,3+,4-,5-/m1/s1
InChIKey=SRBFZHDQGSBBOR-KKQCNMDGSA-N
β-mannose: InChI=1S/C6H12O6/c7-1-2-3(8)4(9)5(10)6(11)12-2/h2-11H,1H2/t2-,3-,4+,5+,6-/m1/s1
InChIKey=WQZGKKKJIJFFOK-RWOPYEJCSA-N
β-acetylglucosamine: InChI=1S/C8H15NO6/c1-3(11)9-5-7(13)6(12)4(2-10)15-8(5)14/h4-8,10,12-14H,2H2,1H3,(H,9,11)/t4-,5-,6-,7-,8-/m1/s1
InChIKey=OVRNDRQMDRJTHS-FMDGEEDCSA-N
Henry Rzepa responded on 22 Feb 2014 at 12:07 pm #
123,000 geometry optimizations is indeed impressive, but I wondered how many of these expensively obtained coordinates were actually available via supporting information. As far as I can tell about 200, although they do have to be extracted from a single monolithic PDF file first. Each entry has almost no metadata, β-glucose 239 is a typical complete example. If all 123,000 original calculations, complete with metadata were available, it would be a fantastic resource. As it is, converting the 200 or so existing coordinates into a more useful resource would take a bit of effort. I notice for example Steve that although you normally take this effort to include one or two sets of coordinates into your blog, even you have balked at attempting the 200, never mind the 123,000!
Why might it be useful? For example it might be possible to automate a correlation between any one structure and the bond/lone pair alignments present (the anomeric interactions, via eg NBO analysis) and hence perhaps learn something about them? But to do this would probably require either contacting the original authors to see if they could perhaps provide some of the coordinates, or even simply repeating the 123,000 calculations!
I do continue to wonder why the computational chemistry community has hardly adopted the use of proper digital repositories for this purpose? The reasons must be largely social rather than technical?