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Preface
N U C L E I C A C I D S were originally conceived purely as carriers of genetic information in the form of the genetic code. D N A was the repository of genetic information, and R N A served as a temporary copy to be decoded in the synthesis of proteins. The discovery of transfer R N A , the "adapter" molecules that assist in the decoding of genetic messages, broadened awareness of the role of R N A . In the past few years, we have come to appreciate the functional versatility of nucleic acids and their participation in a wide range of vital cellular processes. A s new functions for nucleic acids have been identified and characterized, large numbers of sequences have been determined—so-called primary structural information. The determination of three-dimensional structures, however, has not kept up with the accumulation of primary sequence data. Thus, there is intense interest in developing reliable methods of predicting the three-dimensional structures of polynucleotides based primarily on sequence information, supplemented by readily executed experiments. A l l efforts directed at elucidating the three-dimensional structure of a nucleic acid molecule on the basis of readily determined sequence data may be broadly defined as "molecular modeling". A n intermediate step between primary structure and three-dimensional structure is the determination of secondary structure—the pattern of hydrogen-bonded basebase interactions (base pairing) in a molecule. A hierarchical view of nucleic acid structure views primary structure as determining secondary structure. Tertiary structure emerges as secondary structure elements interact with each other. This book was developed from a symposium presented at the 213th National Meeting of the American Chemical Society, titled "Molecular Modeling and Structure Determination of Nucleic Acids", sponsored by the A C S Division of Computers in Chemistry, in San Francisco, California, A p r i l 13-17, 1997. Our aim in organizing the symposium was to bring together scientists who are employing a variety of theoretical and experimental approaches to understand the structure and dynamics of nucleic acids, D N A , and R N A , with the goal of better understanding biological function. This volume contains contributions that represent the breadth of approaches presented at the symposium. A s discussed in the overview, the synergistic interplay of theoretical molecular modeling approaches and experimental structure determination methods was decisive in the success of Watson and Crick in defining the double helix. A s evidenced by the work presented in the symposium, this synergism continues unabated and may be identified as a common underlying theme of this volume. ix
Leontis and SantaLucia; Molecular Modeling of Nucleic Acids ACS Symposium Series; American Chemical Society: Washington, DC, 1997.
Other themes that emerged during the symposium included the urgency of dealing with the problem of conformational flexibility and heterogeneity i n nu cleic acids, particularly for N M R structure determination; the value of treating electrostatic interactions as accurately as possible, and the recent success of the particle mesh Ewald (PME) method in this regard; the need to consider kinetic factors i n modeling the final folded conformations of large structures, i n addi tion to purely energetic factors; and, as already mentioned, the value of a hierar chical approach to three-dimensional structure. It is our hope that this volume will introduce the reader to the wide range of approaches used i n modeling nucleic acid structures, the insights into biological function gained by structural and dynamical studies, and the strong interplay between theoretical and experimental methods. Acknowledgments We acknowledge the financial support for the symposium provided by the fol lowing organizations: the American Chemical Society Petroleum Research Fund (Grant #32048-SE), Glaxo Wellcome, Isis Pharmaceuticals, Molecular Simula tions Inc., and Parke-Davis. W e thank all the participants, and, in particular, Stephen Harvey, for suggestions on ways to broaden the scope of the sympo sium. W e thank Vassiliki Leontis and Holly SantaLucia for their support, pa tience, and encouragement. J. SantaLucia, Jr., acknowledges the support of the Department of Chemistry of Wayne State University. NEOCLES B. LEONTIS
Department of Chemistry Bowling Green State University Bowling Green, OH 43403 JOHN SANTALUCIA, JR.
Department of Chemistry Wayne State University Detroit, MI 48202 September 2, 1997
χ Leontis and SantaLucia; Molecular Modeling of Nucleic Acids ACS Symposium Series; American Chemical Society: Washington, DC, 1997.
