GALILEO GALILEI FOUNDATION
WORLD FEDERATION OF SCIENTISTS
ETTORE MAJORANA CENTRE FOR SCIENTIFIC CULTURE

GALILEO GALILEI CELEBRATIONS
Four Hundred Years Since the Birth of MODERN SCIENCE

INTERNATIONAL SCHOOL OF CRYSTALLOGRAPHY

24th Course: EXPERIMENTAL AND COMPUTATION APPROACHES TO STRUCTURE-BASED DRUG DESIGN

A NATO Advanced Study Institute

ERICE-SICILY: 8 - 19 MAY 1996

Sponsored by the:

• International Union of Crystallography
  
• Italian Ministry of Education
  
• Italian Ministry of University and Scientific Research
  
• Italian National Research Council
  
• Sicilian Regional Government
  

PROGRAMME AND LECTURERS

SMALL MOLECULE CRYSTALLOGRAPHIC STUDIES OF RECEPTOR LIGANDS (DRUGS)

Introduction to use of crystallographic information from ligands and their intermolecular interactions in understanding drug-receptor binding

MACROMOLECULAR CRYSTALLOGRAPHY

Introduction to protein crystallography and the types of information available from structural studies of protein-ligand complexes

CRYSTALLOGRAPHIC DATABASES

Introduction to the use of crystallographic databases with particular emphasis on the advantages of combining macromolecular and small molecule information

COMPUTATIONAL STUDIES OF MOLECULES

Introduction to several computational approaches to studies of drug-receptor interactions, including molecular dynamics, molecular docking, modelling lead compounds, comparisons of molecular shapes

COMPUTER AND DATABASE USE IN DRUG DESIGN

Presentation and hands-on use of several modelling packages which will be supplied by and tutored by vendors. Students will be assigned group projects in the design of drugs for various pharmaceutical targets and will have opportunities to use each software product during the Course

MOLECULAR COMPARISONS

Presentation of several different approaches to comparing molecules including crystallographic packing analysis, molecular scene analysis and artificial intelligence approaches

INTERACTIONS BETWEEN THE MACROMOLECULAR TARGET AND THE LIGAND

Examples of drug design in cases where the structure of the target is known

LIGAND STUDIES

Presentations of structure-activity relationship studies of receptor ligands

ANTIVIRAL AGENTS

Advances in the treatment of immune system diseases including HIV as examples of the power of full integration of all approaches

COMPUTATIONAL APPROACHES

Presentation of recent advanced work in applying molecular modelling and artificial intelligence to drug design

• F.H. ALLEN, Crystallographic Data Centre, Cambridge, UK
  
• E. BENEDETTI, University of Naples, Italy
  
• T.L. BLUNDELL, Birkbeck College, London, UK
  
• N.N. BORKAKOTI, Roche Products Ltd.,Welwyn Garden City, UK
  
• P.M. COLMAN, CSIRO, Parkville, Victoria, Australia
  
• W.L. DUAX, Hauptman-Woodward Medical Research Inst., Buffalo, NY, USA
  
• P.M.D. FITZGERALD, Merck Research Labs, Rahway, NJ, USA
  
• G. FOLKERS, ETH Pharmazie, Zürich, Switzerland
  
• P. GROOTENHUIS, N.V. Organon, Oss, The Netherlands
  
• T. HENDRICKSON, Agouron, San Diego, CA, USA
  
• W.G.J. HOL, University of Washington, Seattle, WA, USA
  
• G. KLEBE, BASF AG, Ludwigshafen am Rhein, Germany
  
• P. KROGSGAARD-LARSEN, Royal Danish Sch. of Pharmacy, DK
  
• R. PAUPTIT, Zeneca, Cheshire, UK
  
• D.C. ROHRER, The Upjohn Co., Kalamazoo, MI, USA
  
• B.K. SHOICHET, Northwest Univ. Med. School, Chicago, IL, USA
  
• J.P. SNYDER, Emory University, Atlanta, GA, USA
  
• M.J.E. STERNBERG, Imperial Cancer Research Fund, London, UK
  
• R.M. STROUD, University of California, San Francisco, CA, USA
  
• R.C. WADE, EMBL, Heidelberg, Germany
  
• K. WATSON, University of Oxford, UK
  

PURPOSE OF THE COURSE

Advances in biotechnology have increased knowledge of medically relevant receptors and enzymes and facilitated a rapid expansion in the number of structures of macromolecules. Coupled with these advances are an exponential expansion in the crystallographic data of drug molecules, introduction of computer searchable databases of precise structural information, development of computational simulations of molecular shape and interactions, and the advent of machine learning and other automated analytical tools to process structural and activity data. These tools form the basis of an emerging field of structure-based drug design: the development of new pharmaceuticals based on observed structures and intermolecular interactions. Drug design strategies will advance most quickly if scientists in these fields understand one another and collaborate to extract maximum advantage from the biotechnology and information science advances.

This Course will provide participants with an overview of drug and macromolecular crystallography and molecular computational methods with the aim of achieving a mutual understanding of the advantages and assumptions of the various methods. Instructions will be delivered in several formats. Recent research results will be presented and discussed to demonstrate the application of the methods taught in the Course and practiced in the group tutorials. Young and expert scientists from the fields of crystallography, information science, pharmacology, biochemistry and computational chemistry are invited to apply.

Group Photo

DIRECTOR OF THE COURSE: P.W. CODDING

DIRECTOR OF THE SCHOOL: T.L. BLUNDELL

DIRECTOR OF THE CENTRE: A. ZICHICHI