Pharmacophore Modeling / Docking / Fragment-Based Design / Scaffold Replacement / R-Group Screening / Project Search / Protein-Ligand Interaction Fingerprints (PLIF)

This workshop explores advanced structure-based drug design (SBDD) workflows used in drug discovery projects. Participants will learn about key topics, including pharmacophore query generation, protein-ligand docking, scaffold replacement, and R-group screening. The session will cover the application of pharmacophore searching in drug design, as well as methods for querying 3D project databases. Additionally, participants will generate and analyze protein-ligand interaction fingerprints (PLIF) to support their design strategies.

Ternary Complex Analysis / Method 4B / Degrader Scoring / Fragment-Based Linker Design / Combinatorial Library Enumeration (CLE)

This workshop explores the use Method 4B, our novel computational workflow to generate ternary complex models formed by heterobifunctional degraders. An initial library of bifunctional degraders will be screened and scored, and the most promising of these initial candidates will be identified for further development. Structure- and fragment-based design tools will be applied to further optimize this degrader. Finally, our web-based Combinatorial Library Enumeration tool will be applied to generate additional candidate degrader molecules.

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.

Alignments and superposition / Loop and linker modeling / Protein-Protein docking / Protein-Ligand Interaction Fingerprints (PLIFs) / Epitope analysis / Homology modeling / Solubility analysis / QSAR modeling / 2D hot spot mapping

This workshop covers essential methods for aligning protein sequences, superposing structures, loop modeling, building fusion protein models, and conducting protein-protein docking. Participants will learn techniques for grafting and refining antibody CDR loops, as well as using a knowledge-based approach to scFv fusion protein modeling with the Linker Modeler application. The session will also cover protein-protein docking of an antibody to an antigen and epitope mapping. Finally, the workshop will guide participants through a complete workflow for generating a QSAR model to predict and analyze protein/biologics solubility.

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.

Molecular surfaces and maps / Ligand interactions / Torsion Analysis / Ligand optimization / Capturing design ideas / Docking / Protein alignments and superposition

This workshop 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. Important milestones will be recorded through Capture for review and to allow for sharing the design session with colleagues. 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.

Sequence alignments / Structure superposition / Multimer alignments and superposition / Homology modeling / Loop modeling / Loop conformational searching

This workshop covers key techniques in protein alignments, superpositions, and homology modeling using MOE. Participants will explore the complete sequence-to-structure workflow in homology modeling, including template searching, query alignment, model building, and refinement, as well as methods for assessing model quality. The session will also delve into protein loop refinement using the Loop Modeler and LowModeMD conformational searching. Protein contacts will be evaluated following the alignment and superposition of protein multimers.

MOE databases / Molecular descriptors / Database filters / Sorting and coloring / Plots / Clustering / Diverse subset selection / QSAR modeling / Binary QSAR / Substructure searching / Molecular fingerprints / Similarity searching

This workshop describes cheminformatics methods for managing and analyzing datasets of small molecules, as well as generating quantitative structure-activity relationship (QSAR) models. Participants will learn how to import data, prepare MOE databases, calculate molecular descriptors, and analyze trends using sorting, coloring, and plotting tools. Advanced database filtering, data clustering, and diverse subset selection techniques will also be explored. The workshop will include sessions on developing both linear regression and binary QSAR models. Finally, data mining of large compound libraries will be demonstrated using substructure and molecular fingerprint similarity searching.