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.