Chemical and Biological Engineering Publications Chemical and Biological Engineering 2002 MM# Modeling of Aldopentose Pyranose Rings Michael K. Dowd United States Department of Agriculture William M. Rockey Iowa State University Alfred D. French United States Department of Agriculture See next page for additional authors Follow this and additional works at: http://lib.dr.iastate.edu/cbe_pubs Part of the Biochemical and Biomolecular Engineering Commons, and the Biological Engineering Commons The ompc lete bibliographic information for this item can be found at http://lib.dr.iastate.edu/ cbe_pubs/31. For information on how to cite this item, please visit http://lib.dr.iastate.edu/ howtocite.html. This Article is brought to you for free and open access by the Chemical and Biological Engineering at Iowa State University Digital Repository. It has been accepted for inclusion in Chemical and Biological Engineering Publications by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. MM# Modeling of Aldopentose Pyranose Rings Abstract MM3 (version 1992, ϵ=3.0) was used to study the ring conformations of d-xylopyranose, d-lyxopyranose and d-arabinopyranose. The nee rgy surfaces exhibit low-energy regions corresponding to chair and skew forms with high-energy barriers between these regions corresponding to envelope and half-chair forms. The lowest 4 energy conformer is C 1 for α- and β-xylopyranose and α- and β-lyxopyranose, and the lowest energy 1 conformer is C 4 for α- and β-arabinopyranose. Only α-lyxopyranose exhibits a secondary low-energy region 1 ( C 4) within 1 kcal/mol of its global minimum. Overall, the results are in good agreement with NMR and crystallographic results. For many of these molecules, skew conformations are found with relatively low 2 1 energies (2.5 to 4 kcal/mol above lowest energy chair form). The S O and C 4conformers of crystalline benzoyl derivatives of xylopyranose are in secondary low-energy regions on the β-xylopyranose surface, 4 within 3.8 kcal/mol of the global C 1 minimum. Disciplines Biochemical and Biomolecular Engineering | Biological Engineering | Chemical Engineering Comments This is a post-print of an article from Journal of Carbohydrate Chemistry, 21, no. 1–2 (2002): 11–25, doi: 10.1081/CAR-120003735. Authors Michael K. Dowd, William M. Rockey, Alfred D. French, and Peter J. Reilly This article is available at Iowa State University Digital Repository: http://lib.dr.iastate.edu/cbe_pubs/31 MM3 MODELING OF ALDOPENTOSE PYRANOSE RINGS Michael K. Dowd,"·" William M. Rockey,ll Allred 0. French/' and Peter J. Reinyll asouthern Regional Research Center, ARS, USDA, 1100 Robert F.. Lee Blvd., New Orleans~ LA 70179, USA bDepartment of Chemical Engineering, Iowa State University, Ames) IA 50011~ USA ABSTRACT MM3 (version 1992, e = 3.0) was use.d to study the ring conformations of Dqxylopyranose, n­ lyxopyranose and D-arabinopyranose. The energy surfaces exhibit low-energy regions corresponding to chair and skew forms with high-energy barriers between these regions 4 corresponding to envelope and half-chair forms. The lowest energy conformer is C1 for a~ and 1 ~~-xylopyranose and a- and ~lyxopyranose, and the lowest energy conformer is c4 for a- and ~-arabinopyranose. Only a-lyxopyranose exhibits a secondary low-energy region ec-~) within 1 kcallmo! of its global minimum. Overa.Jl) the results are in good agreement with NMR and crystallographic results. For many of these molecules, skew conformations are found with 2 relatively low energies (2.5 to 4 kcal/mol above lowest energy chair form). The S0 and 'c~ conform<:rs of crystalline benzoyl derivatives ofxylopyranose axe in secondary low-tmergy 4 regions on the ~-xylopyranose surface, within 3.R kcat!moi of the global C1 minimum. 2 INTRODUCTION Previously, we modeled the pyranosy! ring shapes of the D-aldohexoses with the molecular mechanics progr.m1 MM3. 1 In general, MM3 predicted the shapes ofthes~ cydic structures well. AU of the p-anomers favored the 4C1 conformation, as did most of the a~anomcrs. For the hexoscs existing in multiple forms, e.g. a-idopyranosc and cx-aJtropyranose, the model predicted multiple forms. However, the conformer distribution predicted for these molecules was not always in exact agreement with the distributions predicted from NMR results, signifYing the effects of modeling error, including neglected solvation and entropic effects. In addition, a comparison of the predicted energies for the 'momers indicated that the equatorially configured P-structures were systematically ovcrprcdictcd. A better test of a potential energy function for predicting carbohydrate ring forms would be a series of pyranosyl structures known to be more variable in conformational preference. The aldopyranosyl pentoses, which lack the bulky hydroxymcthy1 group, represent such a series. By NMR,2..3 a.~ and p-xylopyranose and P-lyxopyranose exist predominately in the 4C1 fom1; a.- and ~-arabinopyranose exist predominately in the I ('4 form; and a-lyxopyranosc exists as a mixtur.: of the two chair forms. Ribopyranose, which has already been studied with MM3,4 is also found as a mixture of chair forms. This series appears to be a good test of the ability of potential functions to reproduce ring conformations. In addition to the goal of validating molecular models, there is interest in understanding how saccharides interact with proteins and how these interactions facilitate enzyme kinetics. in part, 3 this stems from the need to improve en:zyme stability or to alter reaction conditions. Xylanase is of commercial interest because it reduces the need for chlorine bleaching in paper pulping. 5.6 A number ofxylanase structures with xylan fragments or related derivatives bound to the active site have now been solved by diffraction crystallography, and these structures suggest that bound 7 9 xlyose rings can have non-chair conformations during hydrolysis. - An understanding of the confbnnational preferences of xylopyranose may be important for understanding the activity and specificity of these enzymes. METHODS The computational methods used in this work have been described in previous publications and 1 4 will only be outlined here. ' To be consistent with those calculations, the 1992 version of MM3 1o- 12 was used -with an elevated dielectric constant (e = 3.0). The elevated dielectric constant was used to reduce the strength of intramolecular hydrogen bonding and better mimic carbohydrates in condensed-phase systems. 13 Planar ring structures were initially generated with PC-Model (Serena Software, Bloomington, IN). These structures were then used to create puckered rings by moving three alternating ring atoms and their connected substituents perpendicular to the initial ring plane. This was accomplished by orienting the planar ring into the xy-plane and adjusting the z-coordinates of the atoms to be shifted. The atoms were moved over a runge of -0.8 A to +0.8 A in 0.1 A increments, which was sufficient to cover all likely ring shapes. For each riug, all three staggered gauche conformations of the four :secondary hydroxyl groups were also varied. Combined with the different combinations of ring shape, this yielded a total of 397,872 (173 x 3~) starting st.ru<.iures for each monosaccharide. Ring pucker was 4 maintained during the energy minimization by fixing the z-coordin.ates of the six ring atoms. All other degrees of freedom were allowed to relax. These optimizations were conducted with the block-diagonal Newton-R.aphson method (MM3 Option 1) and the default optimization criteria. The system of Cremer and Pople (q, ¢, 0) was used to quantify ring shape.14 From the full set of optimized structw'es, a Pickett-Strauss plate carrtle repre:>entation ( rA 0) of the Cremer and Pople puckering sphere was generatcd. 15 To construct this two-dimensional J .. representation, the data was sorted into 10° x J0° regions of¢ and 6, regardless of the value of q I ' or orientation of lhe individual exocyclic groups. The lowest energy conformer from each region was selected, and the resulting grid ofpoints was plotted using SURFER (Golden Software, Golden, CO). Positions of the characteristic conformers (chairs, boats, skews, etc.) within this two-dimensional space arc shown in Fig. 1. The Pickett-Strauss sur lace distorts some aspects of the puckering sphere. Most affected are the two poles {i.e. the chair conformers), which are transformed into the top and bottom y-axes. In effecl, the points representing the poles are stretched into lines corresponding to the two hori:1.ontnl boundaries. Because the system used to generate the puckered rings evenly samples the puckering sphere, the transformation results in a low density of data points near the two chair regions. This results in some distortion of the contour lines near these boundaries. To fmd local minima, the local low-energy regions were identified from the Pickett-strauss 4 surfaces. Molecules with these ring shnpes were built with all 81 (3 ) sets of staggered exocyclic orientations. All of these structures were freely optimi:1.ed to determine the lowest-energy form. 5 If any of the structures from one local region optimized to a different area of the puckering space, the region wa-. not considered to have a local minimum. The Karplus equations of Haasnoot et a1. 16 were used to calculate proton-proton coupling constants for these structures. The Cambridge Crystal Structure Database 17 was searched to identify related crystal structures. If there were multiple entries within the database, only the most recent determination was included in the analysis, and neutron diffraction determinations were used in preference to x-ray determinations. Structures for compounds containing L~sugars were included after converting the puckering parameters ( tPD = 180° - t/Jr. 01; """ 180° - Or) to account for the change in absolute configuration. The Protein Dala Bank 18 was searched tor stfU(,iures with bound xylose rings.