Using Knime for Glide Ligand Docking provides a convenient way to create synergy by integrating both science and IT into a single platform. Just as science needs to be able to rapidly implement new approaches, analalyze and illustrate data from different perspectives, IT needs to provide reliable, process orientated structures that can be standardized and easily maintained.

Knime is designed to be an open, multi-vendor platform that combines life-science techniques with statistical, data-mining and visualization methods. Our approach opens the way for a multitude of future developments, while staying modular and self-contained.

PyMOL is a sophisticated 3D modeling environment whose most widely used features include molecular animation and the ability to create publication-quality, ray-traced graphics. In this presentation, PyMOL project manager Jason Vertrees provides background information on the program and provides a "how-to" survey of PyMOL's most useful features. Dr. Vertrees will conclude the talk with an overview of resources for PyMOL users.

Application of structure-based drug design to G-protein coupled receptors (GPCRs) has received a major stimulus by the recent availability of several novel x-ray crystal structures of this important class of proteins. In this overview of in-house research and examples from the literature, Applications Scientist Thijs Beuming presents a variety of computational techniques applied to the study of GPCRs, including homology modeling, induced fit docking, structural interaction fingerprints, and molecular dynamics simulations.

Over the course of its existence, Glide has seen continual performance gains between each successive version of the software. In this presentation, product manager Matt Repasky presents an overview of recent Glide advances. Dr. Repasky will discuss the new DockingScore, which can reject false positives by accurately accounting for ligand protonation state penalties, describe improved results for metalloproteins, and will survey the most important new Glide features in Schrodinger Suite 2010. Dr. Repasky will present up-to-date scientific and performance benchmarks, and will also present on the results of work done to port Glide to Microsoft's HPC platform.

In this seminar, Schrödinger Application Scientist Noeris Salam discusses the development and validation of a novel method to develop energetically optimized, structure-based pharmacophores for use in rapid in silico screening. The method combines pharmacophore perception and database screening with protein-ligand energetic terms computed by the Glide XP scoring function to rank the importance of pharmacophore features.

The application of this method, including the results of database screens for known actives, is presented for 30 pharmaceutically relevant crystal structures. The method is compared to three other approaches: pharmacophore hypotheses derived from a systematic assessment of receptor-ligand contacts, Glide SP docking, and 2D ligand fingerprint similarity.

The method developed here shows better enrichments than the other three methods and yields a greater diversity of actives than the contact-based pharmacophores or the 2D ligand similarity. Docking produces the most cases (28/30) with enrichments greater than 10.0 in the top 1% of the database and on average produces the greatest diversity of active molecules. The combination of energy terms from a structure-based analysis with the speed of a ligand-based pharmacophore search results in a method that leverages the strengths of both approaches to produce high enrichments with a good diversity of active molecules.