MOEsaic / R-group analysis / Matched molecular pairs / Similarity and substructure searching / Descriptor calculations / Conformational searching / Molecular alignments / Pharmacophore modeling and searching

This workshop focuses on essential in silico methods for guiding drug discovery projects in the absence of protein structural information. Participants will explore SAR analysis through R-group profiling and matched molecular pairs (MMP) analysis using MOEsaic to determine relationships within a chemical series. The session covers molecular descriptor calculations and their application in identifying property correlations. Additionally, molecular alignments and conformational analyses of a congeneric series will be examined to assess the impact of ligand substituents. The workshop also includes an approach for developing pharmacophore queries and offers guidance on managing and manipulating MOE databases.

Virtual screening compound libraries / Descriptors / Molecular Fingerprints / QSPR modeling / Database filtering / Pharmacophore modeling / Pharmacophore-guided docking / Template-based docking / Compound design

This workshop explores the suite of MOE applications for small-molecule virtual screening. Participants will learn to prepare small-molecule databases for screening, filter databases using substructure matching and property values, and build QSAR/QSPR models and fingerprint similarity models as screening filters. The session will cover creating and searching pharmacophore queries and performing small-molecule docking. A complete virtual screening workflow will be presented, including the creation of de novo structures using MOE’s Scaffold Replacement and Medchem transformation tools.

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.

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.

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

This workshop introduces MOE applications for interactive structure-based design. Participants will explore techniques such as active-site visualization, protein-ligand contact analysis, and ligand modification/optimization within the receptor pocket. Key milestones will be recorded using Capture, enabling review and sharing of design sessions with colleagues. The workshop will also cover the docking module and its application in assessing ligand flexibility. Additionally, a protocol for aligning and superposing protein complexes in the context of protein selectivity will be examined.

Scaffold replacement / Medicinal chemistry transformations / Fragment linking / R-group screening / Ligand growing / Pharmacophores / BREED / Fragment databases

This workshop focuses on fragment-based drug design tools in MOE. Participants will explore combinatorial fragment design and scaffold replacement in the receptor active site, along with strategies for fragment linking and growing. The session will also feature methods for generating closely related derivatives using medicinal chemistry transformations and the reaction-based combinatorial builder. Additionally, participants will learn to apply pharmacophores and 2D/3D descriptors to guide drug design processes.

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 Interaction Analysis / Protein-Ligand Docking / Pharmacophore Modeling / High-throughput Docking / Template-Based Docking / Covalent Docking

This workshop will explore some variants of protein-ligand docking to predict the binding of small-molecule structures to a protein target. Pharmacophore-guided docking will be used to preserve key interactions, whereas template-based docking will efficiently position congeneric series of compounds in the binding site. Reaction-based covalent docking will generate poses for covalently bound ligands. Analysis of docking results and techniques to achieve high-throughput docking will also be addressed.

Scaffold Replacement / Ligand Growing / R-group Screening / Bioisosteric Transformations / Pharmacophore Modeling

This workshop will focus on applications for fragment-based drug design, covering methods such as scaffold hopping, fragment growing and R-group exploration to generate novel compound ideas, then optimize and score the structures in the pocket. The use of molecular descriptors and pharmacophore models to guide these computational methods will also be discussed. In addition, an SBDD method for generating closely related analogs through bioisosteric replacements will be 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 for drug discovery projects, covering a broad range of topics from pharmacophore query generation to protein-ligand interaction fingerprints (PLIF). Participants will learn about the application of pharmacophores in protein-ligand docking, scaffold replacement, and R-group screening. Additionally, the workshop will present a method for querying a 3D project database, as well as techniques for generating and analyzing protein-ligand interaction fingerprints (PLIF).

Protein-Protein Interaction Analysis / Molecular Surfaces / Protein Patch Analysis / Protein Properties / Protein Engineering / Antibody Homology Modeling / Antibody Database / Developability Analysis

Protein Alignments and Superposition / Loop and Linker Modeling / Homology Modeling / Protein-Protein Docking / Epitope Analysis / Protein Properties / Protein Solubility Prediction / Protein Patches (2D and 3D) / Biologics QSAR/QSPR Modeling

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

The workshop describes SBDD workflows in drug discovery projects and encompasses a range of topics from pharmacophore query generation to protein-ligand interaction fingerprints. More specifically, the workshop 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).