NMR Spectroscopy and Computer Modeling of Carbohydrates. Recent Advances

369 Pages·2006·32.67 MB·English

by  Johannes F. G Vliegenthar and Robert J. Woods (Eds.)

NMR Spectroscopy and
Computer Modeling
of Carbohydrates

ACS SYMPOSIUM SERIES 930
NMR Spectroscopy and
Computer Modeling
of Carbohydrates
Recent Advances
Johannes F. G. Vliegenthart, Editor
Utrecht University
Robert J. Woods, Editor
University of Georgia
Sponsored by the
ACS Division of Carbohydrate Chemistry

American Chemical Society, Washington, DC
Library of Congress Cataloging-in-Publication Data
NMR spectroscopy and computer modeling of carbohydrates / Johannes F. G.
Vliegenthart, editor ; Robert J. Woods, editor.
p. cm.—(ACS symposium series ; 930)
"Developed from a symposium sponsored by the Division of Carbohydrate
Chemistry at the 226th National Meeting of the American Chemical Society, New
York, September 7-11, 2003"—T.p. verso.
Includes bibliographical references and indexes.
ISBN 13: 978-0-8412-3953-1 (alk. paper)
1. Carbohydrate—Computer simulation. 2. Nuclear magnetic resonance
spectroscopy.
I. Vliegenthart, J. F. G. II. Woods, Robert James, 1962- III. American Chemical Society.
Division of Carbohydrate Chemistry. IV. Series.
QP519 9.N83N694 2006
612'.015780113—dc22 2005044892
The paper used in this publication meets the minimum requirements of American
National Standard for Information Sciences—Permanence of Paper for Printed Library
Materials, ANSI Z39.48-1984.
Copyright © 2006 American Chemical Society
Distributed by Oxford University Press
ISBN 10: 0-8412-3953-3
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Foreword
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Table of Contents
Preface xi
1 Introduction to NMR of carbohydrates
Johannes F. G. Vliegenthart 1
2 Conformational dynamics of oligosaccharides: techniques and computer simulations
Jennie L. M. Jansson, Arnold Maliniak, Goran Widmalm 20
3 Structure and dynamics of carbohydrates using residual dipolar couplings
James H. Prestegard Xiaobing Yi 40
4 Protein-carbohydrate interactions: a combined theoretical and NMR experimental approach on
carbohydrate-aromatic interactions and on pyranose ring distortion
Jesús Jiménez-Barbero, F. Javier Cañada, Gabriel Cuevas, Juan L. Asensio, Nuria Aboitiz,
Angeles Canales, M. Isabel Chávez, M. Carmen Fernández-Alonso, Alicia García-Herrero,
Silvia Mari, and Paloma Vidal 60
5 Laser photo CIDNP technique as a versatile tool for structural analysis of inter- and
intramolecular protein-carbohydrate interactions
Hans-Christian Siebert, Emad Tajkhorshid, Johannes F. G. Vliegenthart, Claus-Wilhelm von
der Lieth, Sabine André, and Hans-Joachim Gabiu 81
6 Hydroxy protons in structural studies of carbohydrates by NMR spectroscopy
Corine Sandström and Lennart Kenne 114
7 Oligosaccharides and cellulose crystal surfaces : computer simulations
Bas R. Leeflang, J. Albert van Kuik, and Loes M. J. Kroon-Bratenburg 133
8 Biomolecular dynamics: testing microscopic predictions against macroscopic experiments
Andrew Almond 156
9 Structural insights: towards a molecular comprehension of the GH13 amylase specificity
Gwénaëlle André-Leroux 170
10 QM/MM simulations in carbohydrates
Abdul-Mueed Muslim, Jonathan P. McNamara, Hoda Abdel-Aal, Ian H. Hillier, and Richard
A. Bryce 186
11 Predicting the three-dimensional structures of anti-carbohydrate antibodies: combining
comparative modeling and MD simulations
Jane Dannow Dyekjaer and Robert J. Woods 203
12 Carbohydrate structure from NMR residual dipolar couplings: is there a correlation between
lactose's anomeric configuration and its three-dimensional stucture?
Darón I. Freedberg, Susan O. Ano, Scott E. Norris, and Richard M. Venable 220
13 Incorporation of carbohydrates into macromolecular force fields: development and validation
Sarah M. Tschampel, Karl N. Kirschner, and Robert J. Woods 235
14 Docking carbohydrates to proteins: empirical free energy functions
Alain Laederach 258
15 Molecular modeling of carbohydrates with no charges, no hydrogen bonds, and no atoms
Valeria Molinero and William A. Goddard III 271
16 Molecular modeling of retaining glycosyltransferases
Igor Tvaroška 285
17 Two unexpected effects found with 2, 3, 4, 6-tetra-O-methyl-D-gluco-and mannopyranosyl
oxacarbenium ions : an O-2 pseudo-equatorial preference and a large H-2-C-2--O-2-CH syn
3
preference
Andrei lonescu, LiJie Wang, Marek Z. Zgierski, Tomoo Nukada, and Dennis M. Whitfield 302

Autor Index 323
Subject Index 325
Preface
In the past ten years, the interest in the functional and
structural aspects of carbohydrates and glycoconjugates has
increased enormously. Great insights have been made into the
mode of action of glycans in cells, tissues, organs, and organisms.
As more and more information becomes known implicating
carbohydrates in biological function, increasing pressure is placed
on all aspects of biophysical methods to adapt and advance in
order to provide structural insight into the biology of carbohydrates
and conjugated glycans. Many existing tools that have served
admirably to probe structure-function relationships in proteins are
difficult or impossible to apply to complex glycans and
glycoproteins. Established structural methods, such as X-ray
diffraction or NMR spectroscopy also face enormous challenges
when applied to the study of biologically relevant glycans in
glycoproteins.
Although significant improvements in analytical techniques
and instrumentation have reduced the amounts of material needed
for unambiguous determination of the primary structure, still
difficulties exist in obtaining sufficient material of acceptable
purity, due to the presence of microheterogeneity in the glycans
present in glycoproteins. In principle, NMR spectroscopy is well
suited for work with less homogeneous samples, but limitations
associated with molecular weight and intermolecular kinetics
attenuate its application to large glycoproteins or
protein-polysaccharide complexes. In addition, the flexibility of
oligosaccharides, especially those containing 1-6 linkages,
introduces unique challenges in interpreting NMR data in terms of
three-dimensional structures. However, the developments in high-
resolution NMR spectroscopy render it possible to deduce at least
the primary sequences of glycoprotein-derived glycans. NMR
parameters also allow relevant conclusions to be drawn concerning
the confirmation and dynamics of glycans in free or covalently
bound form, this data alone is rarely sufficient to completely
xi
determine the three-dimensional structure. Combination with other
approaches such as molecular mechanics calculations and
molecular dynamics simulations are often indispensable.
To focus the attention of glycoscientists on the scope of present
day NMR spectroscopy for the structural studies of carbohydrates and
glycoconjugates, Chapters 1-7 of this volume are collected, mainly
based on contributions at the American Chemical Society's (ACS)
Tutorial Symposium οn NMR Spectroscopy of Carbohydrates in 2004.
Various NMR techniques and applications are presented as advanced
introductions to the type of problems that can be studied by these
methods. For the functioning of glycans in biological systems,
recognition and interaction phenomena with complementary molecules
are key features. The investigation of such processes is also referred to in
several chapters.
Because of the challenges and limitations of traditional
experimental methods, computational techniques can contribute unique
insight into the relationship between oligosaccharide structure and
biological function. Perhaps in no other field can biomolecular
calculations make as major a contribution; whether they serve to provide
models to assist in the interpretation of otherwise insufficient
experimental data or to provide a priori models for the structure of
oligosaccharides or insight into the mechanisms of carbohydrate
recognition. From the application of quantum mechanics in the study of
carbohydrate-processing enzymes to the classical dynamics simulation of
oligosaccharides and their protein complexes, the range of systems being
examined theoretically is rapidly expanding.
While their promise is great, the potential for computational
methods to provide misleading information must be recognized. When
applied to experimentally underdetermined systems, as is frequently the
case when working with NMR data, the onus is clearly on the theorist to

establish the accuracy and suitability of the chosen computational
method. Biomolecules are dynamic and none more so than
oligosaccharides. Thus, it is imperative that carbohydrate modeling and
methodological development address the temporal properties of these
molecules as well as the spatial properties. Oligosaccharides frequently
populate multiple conformational families, arising from rotation about
the glycosidic linkages, that is, they do not generally exhibit well-defined
tertiary structures. To adequately sample these conformational
properties, which often have lifetimes in excess of 5 ns, requires
xii
extremely long MD simulations to be performed. When combined with
the need to include water molecules explicitly, these simulations become
some of the most demanding of any biomolecular system.
Given their structural diversity and flexibility, it is not surprising
that carbohydrate modeling faces many unique challenges. Examples of
many of these issues were discussed at the ACS Computational
Carbohydrate Chemistry Symposium in 2004 and are highlighted in
Chapters 8-16.
The editors hope that the readers will appreciate the various
contributions and will profit from them in solving structural problems of
glycans. It is a pleasure to thank the Symposium lecturers and the writers
of the chapters for their contributions and efforts.
Johannes F. G. Vliegenthart
Bijvoet Center
Utrecht University
Padualaan 8
NL-3584CH Utrecht
The Netherlands
[email protected]
Robert J. Woods
Complex Carbohydrate Research Center
University of Georgia
315 Riverbend Road
Athens, GA 30602

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