Protein Annotation / Protein Patches / Virtual Mutagenesis / Antibody Homology Modeling / Protein Properties / Developability

The workshop covers the application of computational tools for modeling the structures of antibodies, for humanization, and for optimization of properties to enhance developability. Examples will include the identification of glycosylation sites and analysis of correlated pairs using a specialized antibody database. The calculation of protein properties and their optimization to facilitate developability as a product will also be covered.

MOE Databases / Descriptors / Fingerprints / QSPR Modeling / Pharmacophore Modeling / Template-Forced Docking / Scaffold Replacement / MedChem Transformations

The course 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.

Mixed methods / Quantum Mechanics / Molecular Mechanics / Gaussian / ONIOM

Detailed understanding of electronic effects are critical for properly understanding enzymatic reactions, or processes that occur in solution (as just two examples). However, it remains impractical to apply quantum mechanical (QM) approaches to such large biological systems. As a compromise between computational cost and predictive accuracy, mixed method approaches allow us to rigorously partition a system into regions that are treated classically (using molecular mechanics) and (typically) smaller regions that are treated using QM. This partitioning scheme allows the user to focus the more realistic electronic treatment to where it is most needed, providing the practical balance of accuracy and timeliness. The ONIOM scheme, as implemented in the Gaussian electronic structure package, allows for the partitioning of a system into multiple regions, each of which can employ a different level of theory. In MOE 2020 we have created a simple and intuitive interface to set up ONIOM calculations. Using MOE’s powerful ‘selection language’, the assignment of layers is trivial, as is the creation of all required Gaussian input files. These calculations can leverage the new high-performance compute framework available in MOE 2020 to seamlessly be executed, either locally or remotely, using MOE as a simple front-end to your computational queuing system. During this webinar we will provide a brief theoretical orientation to the ONIOM method, followed by a demonstration of how to set up, execute, and analyze ONIOM calculations directly from within the MOE platform.

Protein-Protein Docking / Molecular Surfaces / Protein Patches / Interaction Fingerprints / Clustering / Epitope Analysis

The MOE Protein docking application is used to map epitopes and other protein-protein interfaces (PPI). This automatically calculates a PPI fingerprint for each pose. The poses are clustered using the fingerprint, and epitope residues are identified from the top ranking clusters. The poses can then be annotated in the MOE Window, for browsing through all the top epitopes.

Macromolecular repository / 3D query searching / Pocket similarity / Display electron density / Central repository / Specialized protein databases

PSILO® is a web-based platform for the deposition and analysis of macromolecular structural information. The workshop will describe the application of PSILO® for mining biomolecular data. Approaches to query generation and search result navigation in PSILO will be covered in detail; for example, 3D contact searching, and protein pocket similarity searching. The PSILO and MOE platforms are tightly integrated, and the ability to perform PSILO search queries directly from within MOE will also be described.

Structure Preparation / Sidechain Rotamer Exploration / Electron Density Maps / X-Ray / CryoEM / Solvent Analysis with 3D-RISM

The course will cover methods for evaluating, analyzing and refining protein models derived from electron density data. Topics related to protein structure preparation and side-chain conformational analysis and placement will be discussed. Visualization and interpretation of electron density maps (X-ray/CryoEM) 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.

Cloud / AWS / HPC / High-Throughput Screening / Large Scale Calculations / SLURM / Amazon Cluster

Running MOE on the AWS cloud might appear intimidating. It involves: installing the server and software, configuring a workload manager, data preparation, data transfer, job submission and data retrieval. In this webinar we will start from a newly created AWS account and show how easy it is to install an elastic compute cluster ready for MOE. Next we will connect the AWS cluster to the MOE HPC infrastructure to submit jobs from different applications (Dock, Protein Design, Ensemble Protein Properties, etc.) right from the graphical user interface of your local MOE installation. We will monitor the jobs and retrieve the results once the calculations have been completed. In the last part of the webinar we then install a single instance of MOE on AWS and use the GUI via the browser.