Irwin D. Kuntz

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In this paper we describe the search strategies developed for docking flexible molecules to macomolecular sites that are incorporated into the widely distributed DOCK software, version 4.0. The search strategies include incremental construction and random conformation search and utilize the existing Coulombic and Lennard-Jones grid-based scoring function.(More)
The DOCK program explores possible orientations of a molecule within a macromolecular active site by superimposing atoms onto precomputed site points. Here we compare a number of different search methods, including an exhaustive matching algorithm based on a single docking graph. We evaluate the performance of each method by screening a small database of(More)
We report on the development and validation of a new version of DOCK. The algorithm has been rewritten in a modular format, which allows for easy implementation of new scoring functions, sampling methods and analysis tools. We validated the sampling algorithm with a test set of 114 protein-ligand complexes. Using an optimized parameter set, we are able to(More)
With an increasing interest in RNA therapeutics and for targeting RNA to treat disease, there is a need for the tools used in protein-based drug design, particularly DOCKing algorithms, to be extended or adapted for nucleic acids. Here, we have compiled a test set of RNA-ligand complexes to validate the ability of the DOCK suite of programs to successfully(More)
Most drugs have been discovered in random screens or by exploiting information about macromolecular receptors. One source of this information is in the structures of critical proteins and nucleic acids. The structure-based approach to design couples this information with specialized computer programs to propose novel enzyme inhibitors and other therapeutic(More)
We have used intramolecular cross-linking, MS, and sequence threading to rapidly identify the fold of a model protein, bovine basic fibroblast growth factor (FGF)-2. Its tertiary structure was probed with a lysine-specific cross-linking agent, bis(sulfosuccinimidyl) suberate (BS(3)). Sites of cross-linking were determined by tryptic peptide mapping by using(More)
The biological activities of proteins depend on specific molecular recognition and binding. Computational methods for predicting binding modes can facilitate the discovery and design of ligands and yield information on the factors governing complementarity. The DOCK suite of programs has been applied to several systems; here, the degree of orientational(More)
Molecular docking is an invaluable tool in modern drug discovery. This review focuses on methodological developments relevant to the field of molecular docking. The forces important in molecular recognition are reviewed and followed by a discussion of how different scoring functions account for these forces. More recent applications of computational(More)
Past efforts to employ a structure-based approach to design an inhibitor of the fusion-inducing conformational change in the influenza virus hemagglutinin (HA) yielded a family of small benzoquinones and hydroquinones. The most potent of these, tert-butyl hydroquinone (TBHQ), inhibits both the conformational change in HA from strain X:31 influenza virus and(More)