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.

PSILO / Central macromolecular repository / 3D Query searching / Pocket similarity / MOE-project / Project search / Organizing and centralizing project data / Protein family modeling

This workshop covers the searching and analysis of structural data in PSILO®, as well as the organization and mining of structural families using MOE-Project. Participants will learn to consolidate macromolecular and protein-ligand structural data, generate and navigate advanced queries, and streamline analysis with 3D contact and protein pocket similarity searches. The session also covers organizing structure-based drug design projects, aligning protein families, configuring MOE-Project databases, and using Protein-Ligand Interaction Fingerprints (PLIF) analysis to compare ligand binding modes. Attendees will gain practical skills for efficient structural data mining and project management.

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.

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.

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.

Protein-ligand interactions / Ligand optimization / Protein-ligand docking / Pharmacophore modeling / Template-based docking / High-throughput screening / Scaffold replacement / R-group exploration / Bioisosteric transformations / Ligand properties

This workshop presents common molecular modeling and design techniques for identifying, optimizing and prioritizing small-molecule drug candidates, using MOE. It covers structure preparation and pocket analysis followed by in situ modification. The workshop explains template-based docking (congeneric series) and pharmacophore-guide docking (preserving key interactions) to predict how small molecules bind to a protein target. It also covers advanced settings for achieving high-throughput docking for screening large databases. This workshop continues with a series of de novo fragment-based drug design applications. It focuses 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 and pharmacophore models to guide the drug design process. Finally, a method for generating closely related analogs through bioisosteric replacements is presented.

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.

Protein-ligand interactions / Ligand optimization / Protein-ligand docking / Pharmacophore modeling / Template-based docking / High-throughput screening / Scaffold replacement / R-group exploration / Bioisosteric transformations / Ligand properties

This workshop presents common molecular modeling and design techniques for identifying, optimizing and prioritizing small-molecule drug candidates, using MOE. It covers structure preparation and pocket analysis followed by in situ modification. The workshop explains template-based docking (congeneric series) and pharmacophore-guide docking (preserving key interactions) to predict how small molecules bind to a protein target. It also covers advanced settings for achieving high-throughput docking for screening large databases. This workshop continues with a series of de novo fragment-based drug design applications. It focuses 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 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 (CLE) / Multi-component reactions sketch / Reagent catalogs filtering

This workshop explores essential web-based methods for guiding drug discovery projects without a known protein structure. It examines SAR analysis through R-group profiling and matched molecular pairs (MMP) analysis, using MOEsaic to identify relationships within a 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.