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.

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.

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

This workshop 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 molecular surfaces and visualizing protein-protein contacts in 3D. Antibody properties will be evaluated using specialized calculated protein property descriptors and analyzing protein patches. The application of protein engineering tools for affinity and property optimization of antibodies in the context of developability will be studied. Antibody homology modeling optimization examples will include identifying glycosylation sites and their selective modification using a specialized MOE Project antibody database. All the steps necessary for high throughput antibody homology modeling workflow from sequence to structure to property calculations for developability analysis will be described.

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 methods for aligning protein sequences, superposing structures, loop modeling, building fusion protein models, and conducting protein-protein docking. In particular, a method for grafting and refining antibody CDR loops and using a knowledge-based approach to scFv fusion protein modeling using the Linker Modeler application will be described. Protein-protein docking of an antibody to an antigen and epitope mapping will also be discussed. Finally, a complete workflow for generating a QSAR model for predicting and analyzing protein/biologics solubility will be described.

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

This workshop covers the suite of MOE applications which can be applied to small-molecule virtual screening. Topics include the preparation of small molecule databases for virtual screening, filtering databases based on substructure matching and property values, building QSAR/QSPR models and fingerprint similarity models as database filters, pharmacophore query creation and searching, and small-molecule docking. These tools are used in conjunction to present a complete virtual screening workflow. The creation of de novo structures using the MOE Scaffold Replacement and MOE Medchem transformation applications is also covered.

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.

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.

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.

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.

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.

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 / Interaction analysis / Patch analysis / Protein contacts / Protein properties / Virtual mutagenesis

The webinar covers methods for analyzing and optimizing peptide-protein interactions in the active site. Using a model system consisting of MDMX protein and a peptide ligand modelled from p53, key contacts and interactions will be identified. Properties of the peptide ligand will be calculated, and opportunities for optimisation of the peptide will be derived by calculating protein patches and other properties for the receptor. We will then see how to mutate the residues in the peptide ligand to optimise binding, both by editing one residue at a time, and by "residue scanning" / virtual mutagenesis, which allows us to investigate the effects of multiple mutations together, thereby identifying beneficial changes.

Antibody Modeling / Capture Design Ideas / Antibody Pharmacophore Virtual Screening / Interactive Database Viewer Property Filter / Protein Docking Validation / Map 2D Protein Patch Differences / Visualize Ensemble Averages

CCG is pleased to announce the 2024 release of the Molecular Operating Environment, MOE. In this webinar we will present new features and enhancements in MOE 2024.06 for biologics applications.

Structure preparation / Sidechain rotamer exploration / Electron density maps / Solvent analysis with 3D-RISM

The webinar will cover methods for evaluating, analyzing and refining protein models derived from X -ray crystallographic data. Topics related to protein structure preparation and side-chain conformational analysis and placement will be discussed. Visualization and interpretation of electron density maps for assessing protein models will be described. The 3D-RISM method for predicting and refining the placement of solvent molecules in protein models will also be presented.

Forcefield Parametrization / Forcefield Development / Forcefield Validation / Atom-type Free Parametrization / AmberEHT Forcefield

A new methodology to determine bonded forcefield parameters is presented. A coordinate-free Hückel calculation is the basis for chemical perception and the results are used in combination with physical chemistry relationships to determine parameters for bond lengths, angles and torsions (with associated force constants). Comparisons to quantum mechanical torsion profiles are presented to validate the resulting parameterizations.

RNA Modeling / Capture Design Ideas / AMBER:EHT Forcefield / High-Throughput Biologics Screening / R-group-Activity-Relationship Heatmaps / Predict ECD and ORD

CCG is pleased to announce the 2024 release of the Molecular Operating Environment, MOE. In this webinar we will present new features and enhancements in MOE 2024.06, extending the suite of computer-aided molecular design applications to include: Capture - Document and Share Design Sessions / Pharmacophore-guided High-throughput Biologics Virtual Screening / Map 2D Protein Patch Differences and Ensemble Averages / Updated Amber: EHT Forcefield Parameters from Atom Hybridization Character / Predict ECD and ORD Spectra to Determine Stereochemistry and Conformational Ensembles / Support for Non-natural RNA Bases, Ribose Backbones, and Ionization/Tautomeric States / Interactive Database Viewer Property Filter