Rational Drug Design

by Truhlar, Donald G.; Howe, W. Jeffry; Hopfinger, A. J.; Blaney, Jeff; Dammkoehler, Richard A.

• ISBN13: 9780387987538
• ISBN10: 0387987533
• Format: Hardcover
• Copyright: 1999-03-01
• Publisher: Springer Verlag

Summary

Drug research and discovery are of critical importance in human health care. Computational approaches for drug lead discovery and optimization have proven successful in many recent research programs. These methods have grown in their effectiveness not only because of improved understanding of the basic science - the biological events and molecular interactions that define a target for therapeutic intervention - but also because of advances in algorithms, representations, and mathematical procedures for studying such processes. This volume surveys some of those advances. A broad landscape of high-profile topics in computer-assisted molecular design (CAMD) directed to drug design are included. Subject areas represented in the volume include receptor-based applications such as binding energy approximations, molecular docking, and de novo design; non-receptor-based applications such as molecular similarity; molecular dynamics simulations; solvation and partitioning of a solute between aqueous and nonpolar media; graph theory; non-linear multidimensional optimization, processing of information obtained from simulation studies, global optimization and search strategies, and performance enhancement through parallel computing.

Table of Contents

Foreword	v
Preface	vii
PANEL DISCUSSIONS
Important current problems in drug design that may be computationally tractable
Panelists:
Dave Doherty
Bill Dunn
Graham Richards
Doug Rohrer
Moderators:	1	(6)
A. J. Hopfinger
W.J. Howe
New problems that should be addressed in the next ten years
Panelists:
Gordon Crippen
Simon Kearsley
Garland Marshall
Phil Portoghese
Moderator:	7	(4)
Jeff Blaney
MOLECULAR PROPERTIES
Matching of chemical and biological structures using subgraph and maximal common subgraph isomorphism algorithms	11	(28)
Peter Willett
Molecular similarity	39	(12)
W. Graham Richards
Daniel D. Robinson
Modeling the effect of solvation on structure, reactivity, and partitioning of organic solutes: Utility in drug design	51	(22)
Candee C. Chambers
David J. Giesen
Gregory D. Hawkins
Christopher J. Cramer
Donald G. Truhlar
Wouter H.J. Vaes
Cell-based methods for sampling in high-dimensional spaces	73	(8)
Jason A. Rush
A preliminary multiobjective analysis of the chemotherapeutic benefits of hairpin-linked polyamides	81	(12)
Wynn L. Walker
David S. Goodsell
Richard E. Dickerson
Elliot M. Landaw
RECEPTOR-BASED MODELING
Using structural information for the creative design of molecules	93	(10)
Colin McMartin
Regine S. Bohacek
GrowMol, a de novo computer program, and its application to thermolysin and pepsin: Results of the design and synthesis of a novel inhibitor	103	(12)
Regine Bohacek
Colin McMartin
Peter Glunz
Daniel H. Rich
Deducing objective site models by mixed integer programming	115	(12)
Gordon M. Crippen
NUMERICAL METHODS
Molecular dynamics information extraction	127	(22)
Dennis Sprous
Weidong Wang
Ganesan Ravishanker
Matthew A. Young
David L. Beveridge
Ionic charging free energies using Ewald summation	149	(14)
Tom Darden
Genetic function approximation: Evolutionary construction of novel, interpretable, nonlinear models of experimental data	163	(28)
David Rogers
Applications of distributed computing to conformational searches	191
Brian T. Luke