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.

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.

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.

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.