Fragment-based methods are increasingly becoming popular for lead design and scaffold-hopping in drug discovery. In this webinar we will provide a brief review of all the fragment based design methods in Discovery Studio, and highlight the well-published and validated MCSS methodology. MCSS is a powerful CHARMm-based method for docking and minimizing small ligand fragments within a protein binding site. This scientific functionality can be accessed through a fully automated workflow with associated analysis and visualization tools. With fragment-based docking, accurate scoring and placement of fragments is crucial. We will present recent validation of MCSS using several protein-fragment complexes and show that MCSS is able to recover and identify the X-ray poses.

Population pharmacokinetics is the study of the sources and correlates of variability in drug concentrations among individuals who are the target patient population receiving clinically relevant doses of a drug of interest. When clinical trials run for many years, it becomes difficult to prepare and aggregate incompatible datasets. Using the disparate population pharmacokinetics application software and gathering their results in a compelling way to take better decisions is another key challenge.

Pipeline Pilot is a scientifically intelligent implementation of a workflow technology known as data pipelining. It allows scientists to construct and execute workflows using components that encapsulate many algorithms. This flexible visual programming language captures and deploys your best-practice processes.

This webinar will highlight the population pharmacokinetics tools and protocols within Pipeline Pilot for incompatible data aggregation and preparation, disparate application software automation and interactive reports deployment.

Antibodies are critical elements of the immune system as a first line of defense against foreign entities. There has been tremendous interest in recent years in applying protein modeling methods to produce models of antibody structures - allowing researchers to understand more about the interactions occuring at the loop regions and guide further experiments such as improvements to binding affinities. This webinar will highlight the tools and protocols within Discovery Studio for antibody modeling and demonstrate how to go from starting antibody sequence to model structure with refined hypervariable loop regions.

Whether you have professional training in macromolecular X-ray crystallography or have a modeling background and want to visualize electron density maps, the new X-ray component collection provides you with a suite of components and protocols used in the X-ray refinement process. The new collection makes use of an improved automated typing engine, provides pre-built protocols for refinement jobs including simulated annealing, contains automatic ligand placement capabilities, as well as various example protocols for automating various processes. If you are a user who is only interested in visualizing electron density maps, the new collection reads PDB formatted reflection data, and will quickly generate electron density maps than can be easily displayed in the Discovery Studio interface. The goal of this webinar will be to provide an overview of the new X-ray collection, and present a few examples of flexible workflows that are now feasible thanks to the integration of X-ray technology to Pipeline Pilot

This presentation will provide a high level overview of Discovery Studio 2.5, Accelrys' computational package for Life Sciences research. This new version of Discovery Studio includes many new features and enhancements which can be grouped according to the following themes:

• Improved support for handling small molecule data sets.
• Improved integration with Pipeline Pilot.
• Usability improvements to the Discovery Studio Client.
• Enhanced configuration of the Discovery Studio Client user interface.
• New scientific functionality in the following areas: Fragment based design; X-Ray structure determination; small molecule conformational analysis; transmembrane protein modeling; forcefield analysis; pharmacophore analysis.

Functionality in these different areas will be covered and demonstrations of key new features will be provided.

Pharmacophore modeling allows molecular modelers to determine the spatial arrangement of chemical features that confer drug activity toward a target receptor. With a validated pharmacophore model, researchers are able to screen databases, score and prioritize potential new ligands, explore multiple ligand alignment/binding modes, perform scaffold hopping, and fragment-based design.

Discovery Studio 2.5 includes the most comprehensive suite of pharmacophore related functionality to date, including ligand-based methods, structure-based design and fragment-based pharmacophores. This presentation will provide an overview to the new enhancements, and showcase the improved usability and workflows

Understanding the interactions that proteins make with other proteins in a cell is of critical importance to understanding processes such as signal transduction, cell regulation, and molecular recognition. Experimental determination of the structures of such complexes is not trivial and consequently recent efforts have focused on computational methods. Protein-protein docking is the task of computationally assembling separate protein structures into protein-protein complexes, which can help to aid rational approaches to disease treatment and drug design. This webinar will focus on the ZDOCK and RDOCK protein-protein docking and refinement functionality in Discovery Studio and present the workflow from input, separate protein components to final refined docked complexes.

Antibodies are critical elements of the immune system as a first line of defense against foreign entities. There has been tremendous interest in recent years in applying protein modeling methods to produce models of antibody structures - allowing researchers to understand more about the interactions occuring at the loop regions and guide further experiments such as improvements to binding affinities. This webinar will highlight the tools and protocols within Discovery Studio for antibody modeling and demonstrate how to go from starting antibody sequence to model structure with refined hypervariable loop regions

Molecular Probes for Receptor Structure and Olfactory Function.
The detection of diverse chemical structures by the vertebrate olfactory system is accomplished by the recognition of odorous ligands by their cognate receptors. We used homology modelling and virtual screening to discover novel high-affinity agonists of an olfactory G protein-coupled receptor that recognizes amino acid ligands. Functional testing of the top candidates validated several agonists with potencies higher than any of the receptor's known natural ligands. Modeling revealed molecular interactions involved in ligand binding and further highlighted interactions that have been conserved in evolutionarily divergent amino acid receptors. Significantly, the top compounds display robust activities as odorants in vivo. Our virtual screening approach should be applicable to the identification of new bioactive molecules for probing the structure of chemosensory receptors and the function of chemosensory systems in vivo.

Transmembrane proteins are very important in pharmaceutical research since transmembrane proteins such as the G protein-coupled receptors (GPCR), are the target for many existing drugs as well as for many drug candidates in development. This seminar will showcase how the set of tools and protocols available in Discovery Studio can be combined in a workflow to construct a homology model of a metabotropic glutamate receptor (Trans-Membrane Domain).

The presentation will be followed by a demonstration