Protein-ligand interactions / Protein-ligand docking / Pharmacophore modeling / Template-based docking / Scaffold replacement / R-group exploration / Bioisosteric transformations / Ligand properties / PLIFs

This workshop presents common molecular modeling and design techniques for identifying, optimizing, and prioritizing small-molecule drug candidates. The workshop begins by describing structure preparation and pocket analysis to understand key protein-ligand interactions. Participants will explore template-based docking of congeneric series and pharmacophore-guide docking (to preserve key interactions) to predict how small molecules bind to a protein target. This workshop also presents a series of de novo fragment-based drug design applications, focusing on scaffold hopping and fragment growing methods to generate novel compound ideas, optimize structures in the pocket, and score them. It also discusses the use of molecular descriptors, protein-ligand interaction fingerprints (PLIFs), and pharmacophore models to guide the drug design process. Finally, a method for generating closely related analogs through bioisosteric replacements is presented.

MOEsaic / Matched Molecular Pairs / R-group analysis / Similarity and substructure searching / Multi-parameter optimization / Free-Wilson analysis / Combinatorial Library Enumeration / Multi-component reactions sketch / Reagent catalogs filtering

This workshop explores some essential ligand-based methods for guiding drug discovery projects. Participants will learn how to efficiently use MOEsaic to perform SAR analyses of compound datasets, using approaches such as R-group profiling and matched molecular pairs (MMP) analysis, to identify relationships within chemical series. The session highlights computational strategies for extracting meaningful insights from structure-activity data to support informed decision-making in drug design. The workshop also introduces the CLE application as a powerful tool for streamlining the search of available reagent catalogs using multi-component chemical reactions. It demonstrates how to apply a reaction both as a query and as a transformation to efficiently enumerate all possible product combinations. The session covers methods for inspecting, filtering, and exporting reagents and products, including catalog IDs, for synthesis.

Protein Engineering / Protein Properties / Protein Contacts / Developability / Molecular surfaces / Hot spot analysis / Antibody modeling

This workshop focuses on structure-based antibody design. Topics such as protein-protein interaction analysis, in silico protein engineering, affinity modeling, and antibody homology modeling will be covered. Participants will explore an antibody-antigen co-crystallized complex by generating and examining molecular surfaces and visualizing protein-protein contacts in 3D. Antibody properties will be evaluated using specialized protein property descriptors and protein patch analysis. The session will also cover the application of protein engineering tools for affinity and property optimization in the context of antibody developability. Additionally, participants will learn to optimize antibody homology models, including identifying glycosylation sites and their selective modification using a specialized MOE Project antibody database. The full workflow for high-throughput antibody homology modeling, from sequence to structure to property calculations for developability analysis, will be demonstrated.

Antibody structure prediction / Conformational ensembles / Descriptor calculations / Property prediction / Developability / Cloud computing

Predicting potential liabilities such as aggregation or viscosity is a key step in monoclonal antibody development. Computational property prediction methods are routinely used in the selection and optimization of candidate antibodies. High-quality property prediction involves prediction of ensembles of 3D structures at specified pH to reduce sensitivity to single conformational states. We will present 3dpredict/Ab, a solution that enables ensemble-based predictions of antibody developability descriptors and putative liabilities. 3dpredict/Ab allows for out-of-the-box SaaS automation and integration of such complex simulations of hundreds or thousands of sequences, making them accessible and efficient.

Structure preparation / Non-natural amino acids / Protein Design / Conformational searching / Distance restraints / Peptide-Protein docking / Protein-Ligand Interaction Fingerprints (PLIFs)

This workshop focuses on methods for analyzing and optimizing peptide-protein interactions in the binding site. Participants will learn peptide-protein structure preparation, peptide sequence optimization using both natural and non-natural amino acids, and perform conformational analysis. Peptide-protein docking will be demonstrated, along with tools for analyzing protein-ligand interactions to assess contact points. Advanced conformational searching techniques using distance restraints will also be described.