Chapter 20
Molecular Mechanics and the Structure of Iduronate-Containing Carbohydrates Downloaded by PENNSYLVANIA STATE UNIV on May 21, 2013 | http://pubs.acs.org Publication Date: July 6, 1990 | doi: 10.1021/bk-1990-0430.ch020
M. Ragazzi, A. Provasoli, and D. R. Ferro Instituto di Chimica delle Macromolecole del CNR, via E. Bassini, 15-1-20133, Milano, Italy Previously, our molecular mechanics studies showed that the iduronate ring can adopt the S (skew boat) conformation. This finding rationalized n.m.r. results for heparin (Hep), dermatan sulfate (DeS) and other compounds in solution. In other work, simultaneous minimization of both intra- and inter-chain energies produced well-resolved structures of synthetic polymers. Here, we apply this minimization method (in the REFINE program) to investigate further the solid -state structures of the above glycosaminoglycans. The results favor the C form of iduronate ring for the isolated, two-fold polyanion helix of Hep, while a l l three ring forms ( C , S , and C ) are compatible with the unit axial rise observed by Mitra et al. i n three DeS allomorphs. In particular, models based on C or the S forms of iduronate rings agreed better with observed structure factors from x-ray fiber diffraction studies of the tetragonal form than did models containing C rings. The simultaneous presence of a l l three ring shapes in crystals of DeS was shown to be possible, even after including solvated sodium ions. While we failed to obtain a clear preference among these structures, we can warn against simplistic interpretation of experimental data. 2
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Molecular mechanics methods based on force-field representations of the energy have been a powerful help in solving and refining a wide variety of molecular structures and have become a common tool for conformational analysis of simple and complex compounds. For the past 15 years, these methods have been applied more to proteins than other biomolecules. Apparently, the numerous single crystal studies of proteins have been an important factor in this orientation of modeling. The 3-dimensional structures of oligo- and poly saccharides often have complicated composition, sequences and branching. Worse, these molecules have usually failed to provide single crystals for diffraction studies and data, i f any, arises from powders or fibers. Analyses of such data are often much less definitive. From the theoretical point of view, the stereoelectronic effects in carbohydrates and the charged groups that are often present make difficult the development of a precise potential 0097-6156/90/0430-0332$06.00/0 © 1990 American Chemical Society
In Computer Modeling of Carbohydrate Molecules; French, A., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1990.
20.
RAGAZZIETAL
Structure of Iduronate-Containing Carbohydrates
set. T h e r e f o r e , a n a l y s i s o f even s m a l l c a r b o h y d r a t e m o l e c u l e s i s difficult. N o n e t h e l e s s , t h e r e has been some p r o g r e s s , m o s t l y u s i n g s i m p l e methods, p o s s i b l y supplemented f o r t h e exo-anomeric e f f e c t b u t based on f i x e d bond l e n g t h s and a n g l e s .
Downloaded by PENNSYLVANIA STATE UNIV on May 21, 2013 | http://pubs.acs.org Publication Date: July 6, 1990 | doi: 10.1021/bk-1990-0430.ch020
Iduronate-Containing
Saccharides i n S o l u t i o n
W h i l e d a t a from n.m.r. i n d i c a t e d t h a t t h e ^C- p r e v a i l s i n s o l u t i o n s of t h e i d u r o n a t e - c o n t a i n i n g s a c c h a r i d e s , p e n o d a t e d a t a was i n t e r p r e t e d t o mean t h a t t h e i s correct. The p o s s i b i l i t y t h a t o t h e r r i n g forms might be p r e s e n t was seldom c o n s i d e r e d . I n one case, a " d i s t o r t i o n " o f t h e c h a i r was i n v o k e d t o e x p l a i n t h e d a t a from i d u r o n a t e - c o n t a i n i n g compounds i n s o l u t i o n t h a t c o u l d n o t be r a t i o n a l i z e d w i t h a m i x t u r e o f t h e two forms ( 1 - 3 ) . Cremer and P o p l e have d e s c r i b e d t h e p u c k e r i n g o f sugar r i n g s i n terms o f p s e u d o - a n g l e s (4,) . When computations a r e done i n c a r t e s i a n coordinates, i t i s p o s s i b l e t o " d r i v e " o r step through values o f t h e Cremer-Pople a n g l e s and m i n i m i z e t h e energy f o r a l l o t h e r conformational v a r i a b l e s . I n a f o r c e - f i e l d s t u d y on t h e
