Torrey Pines Institute for Molecular Studies

About: Torrey Pines Institute for Molecular Studies is a nonprofit organization based out in San Diego, California, United States. It is known for research contribution in the topics: Antigen & T cell. The organization has 2323 authors who have published 2217 publications receiving 112618 citations.

An approach to rapid protein crystallization using nanodroplets

Abstract: An approach that enables up to a two order of magnitude reduction in the amount of protein required and a tenfold reduction in the amount of time required for vapor-diffusion protein crystallization is reported. A prototype high-throughput automated system was used for the production of diffraction-quality crystals for a variety of proteins from a screen of 480 conditions using drop volumes as small as 20 nL. This approach results in a significant reduction in the time and cost of protein structure determination, and allows for larger and more efficient screens of crystallization parameter space. The ability to produce diffraction-quality crystals rapidly with minimal quantities of protein enables high-throughput efforts in structural genomics and structure-based drug discovery.

Dynamics of axisymmetric and poloidal flows in tokamaks

Abstract: As a result of turbulence and finite Larmor radius effects, random radial currents are present in a tokamak plasma and these drive sheared axisymmetric poloidal flows. We model these currents with a noise source with given statistical properties and calculate the linear kinetic response to this source. Without collisions, there is no long term damping of these flows; when collisions are included, poloidal flows are damped. The mean square potential associated with these flows is given in terms of the linear response function we calculate and a model correlation function for the current source. Without collisions, the mean square flow increases linearly with time, but with collisions, it reaches a steady state. In the long correlation time limit, the collisionless residual flows are important in determining the mean square flow.

Ligand docking and structure-based virtual screening in drug discovery.

Abstract: Ligand-docking-based methods are starting to play a critical role in lead discovery and optimization, thus resulting in new 'drug-candidates'. They offer the possibility to go beyond the pool of existing active compounds, and thus find novel chemotypes. A brief tutorial on ligand docking and structure-based virtual screening is presented highlighting current problems and limitations, together with the most recent methodological and algorithmic developments in the field. Recent successful applications of docking-based tools for hit discovery, lead optimization and target-biased library design are also presented. Special consideration is devoted to ongoing efforts to account for protein flexibility in structure-based virtual screening.

"Libraries from libraries": chemical transformation of combinatorial libraries to extend the range and repertoire of chemical diversity

Abstract: The generation of diverse chemical libraries using a "libraries from libraries" concept is described. The central features of the approaches presented are the use of well-established solid-phase synthesis methods for the generation of combinatorial libraries, combined with the chemical transformation of such libraries while they remain attached to the solid support. The chemical libraries that are generated by this process have very different physical, chemical, and biological properties compared to the libraries from which they were derived. A wide range of chemical transformations are possible for peptide-based or other libraries, and an almost unlimited range of useful chemical diversities can be envisioned. In the example presented, the amide functionalities in an existing combinatorial library made up of peptides were permethylated while the library remained attached to the solid-phase support used in its synthesis. After removal of the permethylated mixtures from their solid support, this library, now lacking the typical -CONH- amide bonds of peptides, can be tested in solution with virtually all existing assay systems to identify individual compounds having specific biological activities of interest. An illustration of the use of such libraries is presented, in which the described permethylated library was used to identify individual permethylated compounds having potent antimicrobial activity against Gram-positive bacteria.