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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)
Strategies for computational association of molecular components entail a compromise between configurational exploration and accurate evaluation. Following the work of Meng et al. [Proteins, 17 (1993) 266], we investigate issues related to sampling and optimization in molecular docking within the context of the DOCK program. An extensive analysis of diverse(More)
The 17-juxtamembrane cytoplasmic residues of the polymeric immunoglobulin receptor contain an autonomous basolateral targeting signal that does not mediate rapid endocytosis (Casanova, J. E., G. Apodaca, and K. E. Mostov. Cell. 66:65-75). Alanine-scanning mutagenesis identifies three residues in this region, His656, Arg657, and Val660, that are most(More)
AMPA (alpha-amino-3-hydroxy-5-methyl-4-isooxazole) receptors, a major subtype of ionotropic glutamate receptors (iGluRs), mediate the majority of the fast communication between neurons, and the activity-dependent trafficking of AMPA receptors at synapses plays a role in mammalian learning and memory. Here we describe the design, synthesis, and evaluation of(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)
Until recently, applications of molecular docking assumed that the macromolecular receptor exists in a single, rigid conformation. However, structural studies involving different ligands bound to the same target biomolecule frequently reveal modest but significant conformational changes in the target. In this paper, two related methods for molecular docking(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)