There is no cost to attend but pre-registration is required as seats are limited. Registrations will be processed and accepted first-come, first-served. No previous MOE software experience is required to attend.
Structure-Based Drug Design and Ligand Modification
Molecular Surfaces and Maps / Ligand Interactions / Docking / Ligand Optimization / Ligand Selectivity / Protein Alignments and Superposition
The course covers MOE applications for interactive structure based design. Examples include active site visualization, protein-ligand contact analysis and ligand modification/optimization in the receptor pocket. Use of the docking module and its application to assess ligand flexibility will be discussed. A protocol for aligning and superposing protein complexes in the context of protein selectivity will be studied.
The course describes advanced SBDD workflows in drug discovery projects and encompasses a range of topics from pharmacophore query generation to protein-ligand interaction fingerprints. More specifically, the course will cover the application of pharmacophores in the context of protein-ligand docking, scaffold replacement and R-group screening. A method for querying a 3D project database will also be presented along with the generation and analysis of protein- ligand interaction fingerprints (PLIF).
Antibody Modeling and Protein Engineering
Protein Engineering / Protein Properties / Developability / Hot Spot Analysis / Antibody Modeling / Humanization / Molecular Surfaces
The course covers approaches for structure-based antibody design and includes protein-protein interactions analysis, in silico protein engineering, affinity modeling and antibody homology modeling. The interaction of a co-crystallized antibody-antigen complex will be studied by generating and examining the molecular surfaces and visualizing protein-protein interactions in 3D and 2D. Antibody properties will be evaluated using specialized calculated protein property descriptors and analyzing protein patches. The application of protein engineering tools for homology modeling and conducting property optimization of antibodies in the context of developability will be studied. Antibody optimization examples will include identification of glycosylation sites and analysis of correlated pairs using a specialized antibody database. An approach for humanizing antibody homology models will be discussed. All the steps necessary for producing and assessing antibody homology models will be described.
Biologics: Protein Alignments, Modeling and Docking
Protein Alignments and Superposition / Loop and Linker Modeling / Homology Modeling / Protein- Protein Docking / Protein Solubility Analysis / 2D Hot Spot Mapping / PLIF / Biologics QSAR Modeling
The course covers methods for aligning protein sequences, superposing structures, homology modeling fusion proteins and conducting protein-protein docking. In particular, an approach for aligning and superposing multiple structures will be described for determining structural and surface protein variations in relation to protein property modulation. A method for grafting and refining antibody CDR loops as well as using a knowledge-based approach to scFv fusion protein modeling using the MOE linker application will be described. An approach to generate homology models of a murine antigen structure from a human template as well as protein-protein docking of an antibody to an antigen will be discussed. A QSAR model for predicting and analyzing protein/biologics solubility will be described.
The course describes computational SBDD workflows aimed at advancing medicinal chemistry campaigns. Using real examples, attendees will learn how to search databases of structural families to analyse protein-ligand interaction patterns and use these, and pharmacophore constraints, to guide docking.
The course demonstrates how Lead Optimization can be advanced by performing scaffold replacement and medchem transformations on a ligand within the context of a receptor pocket. Transformations sourced from real chemical reactions are used alongside structural constraints to produce libraries of compounds that may enhance binding.