Proceedings of the Nineteenth Jerusalem Symposium in Quantum Chemistry and Biochemistry, held in Jerusalem, Israel, May 5-8, 1986

The Twenty Sixth Jerusalem Symposium reflected the high standards of these distinguished scientific meetings, which convene once a year at the Israel Academy of Sciences and Humanities in Jerusalem to discuss a specific topic in the broad area of quantum chemistry and biochemistry. The topic at this year's Jerusalem Symposium was reaction dynamics in clusters and condensed phases, which constitutes a truly interdisciplinary subject of central interest in the areas of chemical dynamics, kinetics, photochemistry and condensed matter chemical physics. The main theme of the Symposium was built around the exploration of the interrelationship between the dynamics in large finite clusters and in infinite bulk systems. The main issues addressed microscopic and macroscopic sol vation phenomena, cluster and bulk spectroscopy, photodissociation and vibrational predissociation, cage effects, interphase dynamics, reaction dynamics and energy transfer in clusters, dense fluids, liquids, solids and biophysical systems. The interdisciplinary nature of this research area was deliberated by intensive and extensive interactions between modern theory and advanced experimental methods. This volume provides a record of the invited lectures at the Symposium.

The third and last volume of this treatise IS concerned with important applications of the quantum~theory of chemical reactions to chemisorption, catalysis and biochemical reactions. The book begins with an important paper devoted to the theoretical background of heterogeneous catalysis. It is followed by two papers showing typical applications of wave mechanics to the analysis of chemisorption. Catalysed gas-solid reactions are chosen to illustrate gas, organic solid state reaction and some aspects of the mechanism of the FISCHER-TROPSCH synthesis are presented. The second part of the book is devoted to biochemical applications of quantum chemistry. Two papers are concerned with the quantum theory of enzyme activity. Two others present recent progress of quantum pharmacology. Finally an important contribution to the theory of intermolecular forces is made in the view of possible applications to biochemical problems. vii R. Daudel, A. Pullman, L. Salem, and A. Viellard reds.), Quantum Theory o/Chemical Reactions, Volume III, vii. Copyright (c) 1982 by D. Reidel Publishing Company. THEORETICAL BACKGROUND OF HETEROGENEOUS CATALYSIS J.E.Germain Laboratoire de Catalyse Appliquee et Cinetique Heterogene L. A. 231 du Centre National de la Recherche Scientifique Universite Claude Bernard Lyon I, E.S.C.I.L. 43 Boulevard du 11 Novembre 1918, 69622 Villeurbanne Cedex. Heterogeneous Catalysis is a surface Kinetic phenomenon by which a chemical reaction between molecules of a fluid phase is accelerated (activity) and oriented (selectivity) by contact with a solid phase (catalysts, without change of the solid.

Gathering together a number of the best experts in the world, the 27th Jerusalem Symposium was devoted to the theme of the modelling of biomolecular structures and mechanisms. As a result of recent growth in both importance and audience, the papers contained in this volume present a thorough evaluation of the status of the present knowledge in this field. The main topics covered by this year's Symposium include nucleic acids and their interactions, proteins and their interaction, membranes and their interactions, enzymatic processes and the pharmacological and medical aspects of these subjects. Readers will benefit from the interdisciplinary approach which provides an extensive coverage of both theoretical and experimental advances.

One of the central problems in the study of the mechanism of DNA-ligand interactions is the existence and nature of sequence specificity with respect to the base pairs of DNA. The presence of such a specificity could be of particular significance because it might possibly mean the involvement of specific genes in the effectiveness of the different drugs. The elucidation of the factors responsible for the specificity could then be important for the development of compounds susceptible to contribute to the control of gene expression and also to the development of rationally conceived, improved new generations of effective and specific chemotherapeutic agents. Important recent achievements, experimental and theoretical, in the analysis of such sequence specificities open prospects for possible rapid progress in this field. The 23rd Jerusalem symposium was devoted to the exploration of these recent achievements in relation to many types of ligand, with special emphasis on antitumor drugs. All major types of interaction, intercalation, groove binding, covalent linking, coordination, have been considered. So was also the effect of the interaction on the structure and properties of the nucleic acids and the relationship between the interaction and biological or pharmacological activities. We feel that this Volume presents a relatively complete up-to-date account of the state of the art in this important field of research.

The Twenty Fourth Jerusalem Symposium reflected the high standards of these distinguished scientific meetings, which convene once a year at the Israel Academy of Sciences and Humanities in Jerusalem to discuss a specific topic in the broad area of quantum chemistry and biochemistry. The topic at this year's Jerusalem Symposium was mode selective chemistry, which constitutes a truly interdisciplinary subject of central interest in the areas of chemical physics, photochemistry and photobiology. The main theme of the Symposium was built around the exploration of the possibility and conditions for non-statistical reaction dynamics in molecules, van der Waals molecules, clusters and condensed phases. The main issues addressed photoselective and coherent excitation modes, bottlenecks for intramolecular vibrational energy redistribution, the consequences of the internal structure of many-atom systems and of rotational vibrational level structure for intramolecular dynamics, bond selective photodissociation, ultrafast chemical clocks for energy disposal, coherent control of photochemical reactions and nonstatistical unimolecular reaction dynamics. The interdisciplinary nature of this research area was deliberated by intensive and extensive interactions between theory and experiment. This volume provides a record of the invited lectures at the Symposium."

The 25th Jerusalem Symposium represents a most significant highlight in the development and history of these meetings. Living within the decimal system we have celebrated with much pleasure the lath and the 20th Jerusalem Symposia. With this one we experience a feeling of particular satisfaction because 25 years is different from, is more than, two decades and a half. It is a quarter of a century. It seems thus as if we have changed the dimension of our endeavour. In no way do we loose the sense of modesty with respect to the significance of these meetings. For the organizers, however, they do represent a continuity of efforts which we feel happy to have been able to carry out. At this occasion it seems useful to say a few words about the origin of the Jerusalem Symposia and to recall the name of a colleague who played an essential role in their creation and has been a most efficient and devoted co organizer of the seven first of them. This was Professor Ernst Bergmann, one of the most distinguished founders of Israeli Science and a world famous physico-organic chemist.

The second volume of this treatise lS concerned with three important problems: a) environmental effects b) reaction mechanisms c) photochemical processes An important paper is devoted to the solvation problem. The local field representation of surrounding medium effect is analyzed and an application is made to the study of ambident reaction. A paper is devoted to the study of chemical reactivity in inert matrices and a theory of the effect of rare gas matrices on molecules is presented. Six papers are concerned with chemical reactions mechanisms. They are related to migration reactions, nucleophilic additions and electrophilic additions, and homogeneous catalytic reactions. Finally, some aspects of the photochemical processes are discussed. The evolution of electronically excited molecules is analyzed and the natural correlation method is presented. The role of Rydberg states' is photochemistry is suggested, we believe, for the first time. The sudden polarization in olefins is described in a critical way and a new phenomenon is presented: the pho tochemical attachment of aliphatic hydrocarbons to polynuclear aromatic hydrocarbons. vii R. Daudel, A. Pullman, L. Salem, and A. Veillard (eds.;, Quantum Theory of Chemical Reactions, Volume II, vii. Copyright (c) 1980 by D. Reidel Publishing Company. THE SUPERMOLECULE APPROACH TO THE SOLVATION PROBLEM A. PULLMAN Institut de BioLogie Physico-Chimique Laboratoire de Biochimie Theorique, associe au C.N.R.S."

The 11th Jeruaalem SympOlium continued the tradition of the pIe __ t and excitiDs meetiDp wbich 0DCe a year &ather dlJtingni,bed ICientiltl, the wodd's most renowned experts in a specific field of quantum chemistry and biochemistry. in the impressive IUrroundinp of the Israel Academy of Sciences and Humanities. We wiah to thank aU those who made this meetiDg pOllible and contributed to its IUcceSS: the Baron Edmond de Rothschild whOle continuous generosity suarantees the perenniality of our venture, the Israel Academy of Sciences and Humanities and in particu1ar its President Professor A. DvoIItIky, the Hebrew UDivenity of Jerusalem, and Professor David GiDsburg, for their devoted co11aboration. Mn. Abipil Hyam must be thanked for her decisive contribution to the efficiency and IUCcess of the local IIIIII1geDleJlts. Bernard Pulhnan v TABLE OF CONTENTS ~~e v D. G. Gorenstein / P-31 NMR of nucleic acids. Bond angle and torsional effects 1 H. lwahashi and Y. Kyogoku / NMR studies on dynamic properties of nucleic acid base pairs in nonaqueous solvents 17 M. M. Dhingra and R. H. Sarma / NMR studies and minimum energy confonnation calculations on the S'-tenninus of mammalian mRNA 31 H. -D. Ludemann and E. Westho/ / Solution confonnations of purine (JJ) nucleosides and analogs 41 P. Biichner, F. Blomberg, and H. Ruterjans / Nitrogen-IS nuclear magnetic resonance spectroscopy of lSN-Iabeled nucleotides. Investigations of Ribonuclease A -Nucleotide interactions S3 D. B.

The 9th Jerusalem Symposium was dedicated to the memory of Professor Ernst David Bergmann. An imposing and deeply moving memorial session, chaired by Professor Ephraim Katzir, the President of the State of Is rael and a close friend of Professor Bergmann preceded the Symposium itself. During this session, Professor Bergmann's personality, scien tific achievements and contributions to the development of his country were described and praised, besides President Katzir, by Professor A. Dvoretzky, President of the Israel Academy of Sciences and Humanities, Professor D. Ginsburg, Dean of the Israel Institute of Technology in Haifa and the author of these lines. May I just quote short extracts from these speeches. President Katzir: "As we open this ninth in the series of symposia initiated in 1967, it is difficult for me as, I am sure, for many of Ernst Bergmann's friends, co-workers and students, to be here without him. He was not only a great scientist and a beloved teacher, he was one of the most important founders of science in this country. To him we owe many institutes and the establishment here of many branches of science. " Professor Dvoretzky: "Ernst Bergmann's greatness did not stem from one component overshadowing all the others. It was a multifaceted great ness consisting of the harmonious co~lescing of seemingly contrasting entities into a wonderful unity **.

List of the Participants Xl Audience of the Holy Father XVll SCIENTIFIC PAPERS Introductory Remarks. Electrostatics and Specificity III Nucleic Acid Reactions (B. Pullman). . . 1 Theoretical Studies of Molecular Recognition and Ca- lysis by Enzymes (H. A. Scheraga) . . . . 21 Molecular Dynamics of the DNA Double Helix (M. Levitt) 43 Simulating the Energetics and Dynamics of Enzymatic Reactions (A. Warshel) . . . . . . . . . . 59 Structural Studies of DNA-Protein Interactions (B. W. Matthews) . . . . . . . . . . . . . . . . . . . . 83 Protein-Nucleic Acid Interactions, Models and Reality (W. Saenger) . . . . . . . . . . . . . . . . . . . 99 Studying Enzyme-Substrate Interactions by Site-Directed Mutagenesis (A. R. Fersht and G. Winter) . . . . . 123 Sequence Dependence of DNA Conformation, Dynamics and Interactions in Solution (D. ]. Patel, S. A. Kozlowski, A. Pardi, R. Bhatt, S. Ikuta and K. Itakura) 133 Elements of Specific Recognition of Non-Intercalating - gands in the Interaction with DNA (C. Zimmer and G. Luck) . . . . . . . . . . . . . . . . . . . . 175 VIlI PONTIFICIAE ACADEMIAE SCIENTIARUM SCRIPTA VARIA 55 Interactions of Transfer RNAs with their Biological Partners (J. P. Ebel, R. Giege, D. Moras and P. Remy) 207 Antibody Structure and Specificity (D. R. Davies) . 249 Specificity of Ionophore-Cation Interaction (Yu. A. - chinnikov and V. T. Ivanov) " . . . . . . . 263 Theoretical Analysis of Factors Responsible for Specificity in Ionophore-Cation Interactions (A. Pullman) 303 FOREWORD " The specificity of biological interactions" was the subject of a Study Group that met at the Pontifical Academy of Sciences from Novem ber 9-11, 1983. This theme is one of the most advanced fields in modern biology."

This treatise is devoted to an analysis of the present state of the quantum theory of chemical reactions. It will be divided into three volumes and will contain the contributions to an international seminar organized by the editors. The first one, is concerned with the fundamental problems which occur when studying a gas phase reaction or a reaction for which the solvent effect is not taken into account. The two first papers show how the collision theory can be used to predict the behaviour of interacting small molecules. For large molecules the complete calculations are not possible. We can only estimate the reaction path by calculating important areas of the potential surfaces. Four papers are concerned with this important pro cess. Furthermore, in one of these, the electronic reorganization which occurs along the reaction path is carefully analyzed. ~~o papers are devoted to the discussion of general rules as aromaticity rules, symmetry rules. The last two papers are concerned with the electrostatic molecular poten tial method which is the modern way of using static indices to establish relations between structure and chemical reactivity. Volume II will be devoted to a detailed analysis of the role of the solvent and volume III will present important applications as reaction mechanisms, photochemistry, catalysis, biochemical reactions and drug design. SOME RECENT DEVELOPMENTS IN THE MOLECULAR TREATMENT OF ATOM-ATOM COLLISIONS.

The holding of the 8th Jerusalem Symposium was saddened by the sudden death of Professor Ernst D. Bergmann at the very eve of this meeting. With him disappeared one of the leading world scientists in the field of physical chemistry and biochemistry. His innumerable friends and admirers over the whole world mourn him profoundly. All those who knew him personally and among them the participants in the previous Jerusalem Symposia will remember for ever the exceptional qualities of the scientist and the unusual human warmth of the man. With Ernst D. Bergmann the state of Israel lost one of the founders of its Science and one of its most brilliant and renowned representatives. The spirit which he suc ceeded to inoculate into his numerous disciples and pupils will, however, continue to perpetuate his name and his work. The Jerusalem Symposia will continue as a living testimony to his brilliant inspiration. Before dying, Professor Bergmann has prepared a few opening remarks for the 8th Jerusalem Symposium. They are reproduced here. BERNARD PULLMAN OPENING WORDS Prepared by the Late Professor Ernst David Bergmann It gives me great pleasure to welcome you all on behalf of the President and the Rector of the Hebrew University which is co-sponsoring this meeting, and of the President and Council of the Israel Academy of Sciences and Humanities which for the eighth time has put its premises at our disposal."

Bernard PULLMAN During a long period organic chemistry was one of the pre ferred field of exploration for many quantum chemists. It still remains of major interest for a number of them, but altogether it seems as if the center of gravity of the quantum molecular theories became displaced towards different horizons. The dis placement seems in fact to occur in two directions. On the one hand, we see a prominent development of very refined computations for relatively small and frequently inorganic molecular systems with the view of a better and better reproduction of their obser vable properties and thus a better understanding of the fundamen tal principles governing the electronic structure of molecules. On the other hand, there is a no less prominent development of frequently also no less refined computations towards the study of molecular systems which because of their dimensions or the com plexity of the questions which they raise go beyond the usual treatment of organic molecules. These later studies involve in particular the penetration of quantum-mechanical concepts and me thods into the realm of biochemistry, biophysics, and pharma olo gy. It so happens that because of the nature of the problems in volved this penetration has taken up a double aspect."

The Seventeenth Jerusalem Symposium focused on dynamics on surfaces, a subject of interest in the areas of chemistry, physics and material sciences. The Symposium reflected the high standeds of these distinguished scientific meetings, which convene yearly at the Israel Academy of Sciences and Humanities to discuss a specific topic in the broad area of quantum chemistry and biochemistry. Molecule-surface dynamics constitutes a fast developing, current, research area. The main theme of the Symposium was built around a conceptual framework for the elucidation of the chemical and physical aspects of atomic and molecular scattering off surfaces, surface transport, surface reaction dynamics and radiative interactions on surfaces. The interdisciplinary nature of this research area was emphasized by intensive and extensive interactions between scientists from different disciplines and between theory and experiment. HeLd under the auspices of the Israel Academy of Sciences and Humanities and the Hebrew University of JerusaLem, the Seventeenth JerusaLem Symposium was sponsored by the Institut de BioLogie Physico- Chimique (Fondation Edmond de RothschiLd) of Paris. We wish to ex- press our deep thanks to Baron Edmond de Rothschild for his continuous and generous support, which makes him a true partner in this important endeavour. We would aLso like to express our gratitude to the Admi- nistrative Staff of the Israel Academy, and in particular to Mrs. AvigaiL Hyam, for the efficiency and exceLLency of the LocaL arrangements.

th The 16 Jerusalem Symposium debated on one of the most im- portant subjects of modern molecular biology: the nucleic acids. It continued the tradition of gathering the most distinguished experts in the field. Placed under the auspices of the Isra~l Acade~y of Sciences and Humanities and the Hebrew University of Jerusalem it was sponsored by the Institut de Biologie Physico-Chimique (Fondation Edmond de Rothschild) of Paris and the Na~ional Foundation for Cancer Research of Bethesda, U. S. A. We wish to express our deep thanks to the Baron Edmond de Rothschild for his continuous generosity which guarantees the perenniality of these meetings and to the authorities of the National Foundation for Cancer Research, in particular Mrs Tamara Salisbury and Dr. Franklin Salisbury for having joined hands with us in this venture. We wish also to express our gra~itude to the adminis- trative staff of the Isra~l Academy and in particular to Mrs Avigail Hyam for the efficiency and excellency of the local arrangements. Bernard Pullman ,Joshua Jortner B. Pullman and J. Jortner (eds. ) , ,Vucleic Acids the Vectors of Life, /-/5. (c) 1983 by D. Reidel PuhlisliinK Company. BASE SEQUENCE. I-!E. LJY ":'TRIJCTIIR!: I\NI' INTRIN

The seventh Jerusalem Symposium has tried to penetrate into a field of research towards which the efforts of a large number of the most variegated modern techniques are conversing: molecular and quantum pharmacology. The hope to elucidate the mode of action of drugs, to establish correlations between the electronic and con formational structures of drugs and their mode of action and level of activity, to derive from these data the nature of the cellular receptors and an understanding of the interaction of the drugs with those receptors - is a strong stimulus to enlarge and deepen the research efforts with the ultimate view to rationalize the design of more efficient and more specific drugs. The Symposium represents an attempt to survey the progress made so far in this respect and the methods and efforts employed in order to arrive at even greater achievements. The presentation of this Symposium differs somewhat from that of the preceding ones. Owing to the political events which disturbed the peace in the Middle East and therefore the normal activities of commerce and industry in Israel at least temporarily, the printing and distribution of this volume were entrusted to the Reidel Publishing Company. We wish to thank them for their very efficient col1aboration and for all their efforts to publish this volume with a minimum delay."

The Fifteenth Jerusalem Symposium reflected the high standards of the former international scientific meetings, which convene once a year at the Israel Academy of Sciences and Humanities in Jerusalem to discuss a specific topic in the broad area of quantum chemistry and biochemistry. The topic at this year's Jerusalem Symposium was intramo lecular dynamics, a subject of central interest for theoreticians, che mists and biologists. During the last two decades, there has been remarkable pro gress in our understanding of time dependent phenomena. The development and application of the modern techniques of quantum mechanics and sta tistical mechanics to excited-state dynamics and to chemical and biophy sical systems constitutes a fast developing current research area. The main theme of the Symposium was built around a conceptual framework for the elucidation of photophysical and photochemical phenomena in atoms, molecules, van der Waals complexes and clusters, condensed phases, poly mers and biological supermolecules. The interdisciplinary nature of this research field was deliberated by intensive and extensive interactions between scientists from different disciplines and between theory and experiment. This volume provides a record of the invited lectures at the Symposium."

Proceedings of the 10th Jerusalem Symposium on Quantum Chemistry and Biochemistry held in Jerusalem, Israel, March 28-31, 1977

Proceedings of the Third International Congress of Quantum Chemistry, held at Kyoto, Japan, October 29-November 3, 1979

The Fourth International Congress in Quantum Chemistry under the auspices of the International Academy of Molecular Quantum Science in Menton, France was arranged at Uppsala University, Uppsala, Sweden, during the period June 14 - 19, 1982, in close collaboration with the University of Florida. The previous congresses were held in Menton 1973, New Orleans 1976, and Kyoto 1979, and the 1985 congress is tentatively planned to be held in the province of Quebec, Canada. The Congress consisted of six symposia in various areas of quantum chemistry, solid-state theory, and quantum bi ology. The meeting was attended by about 450 scientists from 45 different nations, and a total of more than 300 scientific papers were presented. Even the poster contri butions were given some plenary time. These proceedings contain the text of the plenary lec tures as well as the chairmen's introductions, whereas the contributed papers will be published in the International Journal of Quantum Chemistry, (John Wiley & Sons, New York) in the regular January - April 1983 issues."

The 12th JerusaLem'Symposium was devoted to the exciting sub- ject of CataLysis in Chemistry and Biochemistry. As usuaL in these Sym- posia Theory and Experiment have been considered simuLtaneousLy in dis- cussions> invoLving renowned experts from many countries. We wish to thank aLL those who made this meeting possibLe and contributed to its success: the Baron de RothschiLd whose continuous generosity is at the source of these gatherings, the IsraeL Academy of Sciences and Humanities which offers us the cordiaL hospitaLity of its impressive and beautifuL buiLding and gardens and the Hebrew University of JerusaLem, faithfuL cosponsor of the Symposia. THE MACROMOLECULAR ELECTROSTATIC EFFECT IN BIOCHEMICAL ~EACTIVITY OF THE NUCLEIC ACIDS. BERNARD PULUIAN Institut de BioLogie Physico-Chimique, Laboratoire de Biochimie Theorique, aSSOCle au C. N. R. S. , 13, rue P. et M. Curie, Paris 75005, France. 1. INTRODUCTION The roLe of the macromoLecuLe and of its overaLL structure upon the reactivity of its reaction site(s) represents one of the fundamentaL probLems in the theory of cataLysis. The most impressive and most fre- quentLy considered exampLes occur in the fieLd of proteins where the probLem generaLLy consists of accounting for the enhancement of the reaction rate at the active site or at the coenzyme with respect to modeL systems, devoid of the macromoLecuLar superstructure. Different effects have been considered as possibLy responsibLe for the infLuence of the macromoLecuLe on such LocaLized-site reactions. I do not have the time to summarize or discuss them here.

th The 13 Jerusalem Symposium on Quantum Chemistry and Bio- chemistry was dedicated to the memory of Ernst David Bergmann, one of the founders of this series of Symposia, at the occasion of the 5th anniversary of his death. The opening session was honored by the pre- sence of H. E. Yzhak Navon, President of the State of Israel and of Baron Edmond de Rothschild whose generous and constant support makes these Symposia possible. To both these distinguished guests we address the expression of our deep gratitude. Our thanks are also due to the Israel Academy of Sciences and Humanities, in particular to its President Professor Aryeh Dvoretzky and to the Hebrew University of Jerusalem for their hospita- lity and helpful association. I had the privilege this time to join efforts in the organi- zation of this Symposium with two distinguished American colleagues, Prof. P. O. P. Ts'o from Johns Hopkins University and Dr. Harry Gelboin from the National Institute for Cancer Research. I wish to thank them for their invaluable help and the two Institutions which they repre- sent for important financial support. th The subject of the 13 Jerusalem Symposium brings us back to that of the 1st Symposium held in 1967. The comparison of the two Proceedings enables us to evaluate the important developments which occurred in this field of research during the last 13 years.

The Twentieth Jerusalem Symposium reflected the high standards of these distinguished scientific meetings which convene once a year at the Israel Academy of Sciences and Humanities in Jerusalem to discuss a specific topic in the broad area of quantum chemistry and biochemistry. The Twentieth Jerusalem Symposium marked an auspicious occasion. commemorating two decades of this scientific endeavour. The topic at this year's Jerusalem Symposium was Large Finite Systems which constitutes a truly interdisciplinary subject of central interest in the broad areas of chemistry. physics. astrophysics and biophysics. The main theme of the Symposium was built around bridging the gap between molecular. surface and condensed matter chemical physics. Emphasis was placed on the interrelationship between the properties of large molecules. van der Waals complexes and clusters. focusing on the structure. dynamics of nuclear motion. quantum and thermodynamics size effects. the nature of electronic states and excited-state energetics and dynamics of large finite systems. The interdisciplinary nature of these research areas was deliberated by intensive and extensive interactions between scientists from different disciplines and between theory and experiment. This volume provides a record of the invited lectures at the Symposium.