Ab initio RNA folding

RNA molecules are essential cellular machines performing a wide variety of functions for which a specific three-dimensional structure is required. Over the last several years, experimental determination of RNA structures through X-ray crystallography and NMR seems to have reached a plateau in the number of structures resolved each year, but as more and more RNA sequences are being discovered, need for structure prediction tools to complement experimental data is strong. Theoretical approaches to RNA folding have been developed since the late nineties when the first algorithms for secondary structure prediction appeared. Over the last 10 years a number of prediction methods for 3D structures have been developed, first based on bioinformatics and data-mining, and more recently based on a coarse-grained physical representation of the systems. In this review we are going to present the challenges of RNA structure prediction and the main ideas behind bioinformatic approaches and physics-based approaches. We will focus on the description of the more recent physics-based phenomenological models and on how they are built to include the specificity of the interactions of RNA bases, whose role is critical in folding. Through examples from different models, we will point out the strengths of physics-based approaches, which are able not only to predict equilibrium structures, but also to investigate dynamical and thermodynamical behavior, and the open challenges to include more key interactions ruling RNA folding.Comment: 28 pages, 18 figure

Chemical dynamics

CHEMICAL EDUCATION is changing rapidly, not only because of the explosive growth of knowledge but also because the new knowledge has stimulated reformulation of working principles in the science. Undergraduate curricula and individual courses are in constant flux. Nowhere is the change and challenge greater than in freshman chemistry. Teachers of freshmen must meet the intellectual needs of students who have had more sophisticated and stimulating high school courses than those given a decade ago. At the same time, the freshman teacher must be aware of the constant modification of the more advanced courses in chemistry and other fields that his students will study later. Continuous reformulation of courses sometimes results in the inclusion of valuable new material at the expense of other equally valuable material. We believe that this has happened in some of the sophisticated courses in freshman chemistry. Structural chemistry often receives far greater emphasis than chemical dynamics. In 1965, the Westheimer Report (Chemistry: Opportunities and Needs, National Academy of Sciences, 1965) identified the three major fields of chemistry as structure, dynamics, and synthesis. We firmly believe that a balanced course in general chemistry should reflect the outlook of this report. The study of modern chemical synthesis is too demanding to be covered in depth in an introductory course. However, chemical dynamics -- the systematic study of reactions and reactivity -- can and should be studied at the freshman level. The study of changing chemical systems is the most fascinating part of the field for many students, and its early introduction forms a solid foundation for later study. This small volume is our attempt to answer the need. The book is intended for students who have had introductory stoichiometry, energetics, and structure at the level of a modern freshman textbook (for example, Basic Principles of Chemistry, by H. B. Gray and G. P. Haight, Jr., W. A. Benjamin, Inc., New York, 1961). Chemical Dynamics is designed to accompany approximately 20-25 lectures to be given as the concluding section of a freshman chemistry course. We have chosen topics for their fundamental importance in dynamics and then tried to develop a presentation suitable for freshman classes. Discussion of each topic is limited, because chemistry majors will inevitably return to all the subject matter in more advanced courses. We hope that the following ideas have been introduced with a firm conceptual basis and in enough detail for the student to apply them to chemical reality. 1. Thermodynamics and kinetics are two useful measures of reactivity. 2. Characteristic patterns of reactivity are systematically related to molecular geometry and electronic structure. 3. Reaction mechanisms are fascinating in their own right and indispensable for identification of significant problems in reaction rate theory. 4. The concepts underlying experiments with elementary reaction processes (molecular beams) are simple, even though the engineering of the experiments is complicated. 5. Application of theories of elementary reaction rates to most reactions (slow reactions, condensed media, etc.) provides enough challenge to satisfy the most ambitious young scientist. The book includes exercises at the end of each chapter except the last. Their purpose is didactic, inasmuch as most have been written with the aim of strengthening a particular point emphasized in the chapter, or of introducing an important topic which was not developed in the text for reasons of space and which would normally be taken up in greater detail in later courses. The material in this volume has been adapted primarily from a portion of the lectures given by H.B.G. and G.S.H. to the Chemistry 2 students at the California Institute of Technology during the academic years 1966-1967 and 1967-1968. These lectures were taped, written up by J.B.D., and distributed to the students in the form of class notes. The final manuscript was written after class-testing of the notes. Our decision to revise the Chemistry 2 notes in the form of an introductory text was made after H.B.G. and G.S.H. participated in the San Clemente Chemical Dynamics Conference, held in December 1966 under the sponsorship of the Advisory Council of College Chemistry. At San Clemente we found we were not the only group concerned over the exclusion of significant reference to chemical reactions and reactivity relationships in freshman courses. In addition to their general encouragement, which provided the necessary additional impetus, these colleagues prepared a series of papers for publication in an issue of the Journal of Chemical Education. It is a pleasure to acknowledge here the direct contribution these papers made in shaping the final form of our volume; specifically, in preparing Chapter 6, we have drawn examples from the San Clemente papers of Professors R. Marcus, A. Kuppermann and E. F. Greene, and J. Halpern. The concluding chapter of this book was developed from the lectures given by Professors E. F. Greene (dynamics in simple systems), Richard Wolfgang (atomic carbon), John D. Roberts (nuclear magnetic resonance), and F. C. Anson (electrochemical dynamics) to the students of Chemistry 2 in May 1967. These colleagues have kindly given us permission to use their material. We are grateful to Professors Ralph G. Pearson and Paul Haake, who read the entire manuscript and offered valuable criticism. It is a special pleasure to acknowledge the enormous contribution our students in Chemistry 2 made to the project. Their enthusiastic, critical attitude helped us make many improvements in the manuscript. Thanks are also due to four very special members of the staff of W. A. Benjamin, Inc., for seeing this project through with infectious vigor. Finally, and not the least, we acknowledge the role Susan Brittenham and Eileen McKoy played in preparing the final manuscript. JOSEPH B. DENCE HARRY B. GRAY GEORGE S. HAMMOND Pasadena, California January 196

Synthetic metallomolecules as agents for the control of DNA structure

This tutorial review summarises B-DNA structure and metallomolecule binding modes and illustrates some DNA structures induced by molecules containing metallic cations. The effects of aquated metal ions, cobalt amines, ruthenium octahedral metal complexes, metallohelicates and platinum complexes such as cis-platin are discussed alongside the techniques of NMR, X-ray crystallography, gel electrophoresis, circular dichroism, linear dichroism and molecular dynamics. The review will be of interest to people interested in both DNA structure and roles of metallomolecules in biological systems

Second Symposium on Chemical Evolution and the Origin of Life

Recent findings by NASA Exobiology investigators are reported. Scientific papers are presented in the following areas: cosmic evolution of biogenic compounds, prebiotic evolution (planetary and molecular), early evolution of life (biological and geochemical), evolution of advanced life, solar system exploration, and the Search for Extraterrestrial Intelligence (SETI)

Biophysical and electrochemical studies of protein-nucleic acid interactions

This review is devoted to biophysical and electrochemical methods used for studying protein-nucleic acid (NA) interactions. The importance of NA structure and protein-NA recognition for essential cellular processes, such as replication or transcription, is discussed to provide background for description of a range of biophysical chemistry methods that are applied to study a wide scope of protein-DNA and protein-RNA complexes. These techniques employ different detection principles with specific advantages and limitations and are often combined as mutually complementary approaches to provide a complete description of the interactions. Electrochemical methods have proven to be of great utility in such studies because they provide sensitive measurements and can be combined with other approaches that facilitate the protein-NA interactions. Recent applications of electrochemical methods in studies of protein-NA interactions are discussed in detail

The 1st Symposium on Chemical Evolution and the Origin and Evolution of Life

This symposium provided an opportunity for all NASA Exobiology principal investigators to present their most recent research in a scientific meeting forum. Papers were presented in the following exobiology areas: extraterrestrial chemistry primitive earth, information transfer, solar system exploration, planetary protection, geological record, and early biological evolution

Bioinorganic Chemistry

This book covers material that could be included in a one-quarter or one-semester course in bioinorganic chemistry for graduate students and advanced undergraduate students in chemistry or biochemistry. We believe that such a course should provide students with the background required to follow the research literature in the field. The topics were chosen to represent those areas of bioinorganic chemistry that are mature enough for textbook presentation. Although each chapter presents material at a more advanced level than that of bioinorganic textbooks published previously, the chapters are not specialized review articles. What we have attempted to do in each chapter is to teach the underlying principles of bioinorganic chemistry as well as outlining the state of knowledge in selected areas. We have chosen not to include abbreviated summaries of the inorganic chemistry, biochemistry, and spectroscopy that students may need as background in order to master the material presented. We instead assume that the instructor using this book will assign reading from relevant sources that is appropriate to the background of the students taking the course. For the convenience of the instructors, students, and other readers of this book, we have included an appendix that lists references to reviews of the research literature that we have found to be particularly useful in our courses on bioinorganic chemistry