Schrödinger has developed its Induced Fit Docking methodology to accurately predict ligand binding modes in circumstances where changes to the receptor shape are needed to accommodate the ligand. The method involves a combination of Glide docking using a softened potential, followed by a Prime

protein structure refinement, and finishes with a Glide energy evaluation to obtain the top-scoring ligand-receptor pair. Validation studies have been performed on targets for which standard docking methods fail, and show that Induced Fit Docking can be successfully applied to a wide variety of relevant targets.

The presentation will last about one hour, and includes time for a question-and-answer session.

Matt Repasky, product manager for Glide , will discuss features and capabilities of Schrödinger's docking software, as well as underlying scientific methodologies. Additionally, results from a number of Glide validation studies will be presented, and current development plans will be discussed.

The presentation will last about one hour, and includes time for a question-and-answer session.

The recently developed Quantum Mechanical-Polarized Ligand Docking protocol (QPLD) has been shown to provide significantly enhanced docking accuracy compared to pure force field methods. In this algorithm, fixed charges of ligands obtained from force field parameterization are replaced by QM/MM charges calculations in the protein environment, treating only the ligand as the quantum region. Schrödinger Director of Applications Science Woody Sherman discusses development and validation of QPLD.

The presentation will last about one hour, and includes time for a question-and-answer session.

The theoretical study of biological systems requires an accurate understanding of molecular processes that take place on different time scales. Fast motions, such as those involving a chemical reaction, typically require a quantum mechanical description. Slower motions, responsible for conformational changes, can be modeled using the more approximate method of classical force field potentials. This seminar introduces the results of novel efforts to combine both quantum mechanical and classical approaches using Schrödinger software such as Prime and QSite .

Topics covered include:

• The successful use of mixed quantum mechanical/molecular mechanical methods (QM/MM) to describe bond-breaking and bond-forming events
• The coupling of protein structure prediction algorithms and QM/MM methods to accurately determine how protein conformational changes can result in a reactive chemical process
• The concerted application of protein structure prediction algorithms and QM/MM methods to model the dynamics of protein-ligand binding

The presentation will last about one hour, and includes time for a question-and-answer session.

Dr. Dixon will discuss the features and capabilities of the recently released Phase 2.5, and will present results obtained using advanced functionality.

The presentation will last about one hour, and includes time for a question-and-answer session.

Fragment-based docking is an excellent approach to structure-based drug design when novel chemotypes are required. However, accurately docking small molecule fragments can be a challenging task. In this seminar, Woody Sherman, Schrödinger's Director of Applications Science, describes recent work on fragment docking. Topics covered include the use of QM-Polarized Ligand Docking (QPLD) to accurately place fragments, and how docked fragments can be used to create structure-based pharmacophore models suitable for virtual screening and lead discovery.

The presentation will last about one hour, and includes time for a question-and-answer session.

Dr. Woody Sherman, Schrödinger Director of Applications Science, discusses new software features and programs present in the recently released 2007 Schrödinger Suite.

The presentation will last about one hour, and includes time for a question-and-answer session.

Based on the highly regarded software from Professor Bill Jorgensen's lab at Yale, MCPRO+ is a well-validated simulation package that performs Monte Carlo statistical mechanics simultions of peptides, proteins, and nucleic acids, and calculates free energies of binding using perturbation theory. In this seminar, product manager Dr. Matt Repasky highlights the software's features and capabilities, and presents the results of case studies demonstrating the accuracy of the FEP methodology implemented in the MCPRO+.

The presentation will last about one hour, and includes time for a question-and-answer session.