Understanding the effect of mutation to protein stability and on protein binding affinity is key to designing protein therapeutics and also to explaining the effect of naturally occurring mutations to biological events.  We present two novel CHARMm-based computational protocols to calculate the free energy changes of protein stability and binding affinity resulting from amino acid substitutions1.  In contrast to existing published methods, the temperature dependence of energy contributions is included in the physical model.  This is known to be important in understanding and improving the thermal stability of proteins.  Furthermore, the use of Generalized Born solvation model with implicit membrane2 makes the methods applicable to transmembrane proteins.  The calculations are fast and automated so that not only alanine scanning, but complete amino acid scanning can be performed on large set of residues easily.  Validation results and possible application of the method for the purposes of protein design and bioinformatics are discussed.

The latest release of Accelrys’ Discovery Studio 3.1 builds on the new release of Pipeline Pilot 8.5, providing enhanced scalability and job parallelization capabilities to modeling and simulation studies.  This webinar will provide an overview of the new functionality available in the latest release, including new market-leading tools to predict both the sites and propensity to aggregate in therapeutically important proteins.  Furthermore, we will also showcase enhancements to our free collaboration and visualization tools, further helping scientists to efficiently and effectively share key modeling results with research colleagues.

In the growing area of biologics discovery and development, protein aggregation has become a key area of focus for the successful transition of a therapeutic candidate from the lab into the clinic. Unfortunately, aggregation and protein instability are not unexpected events when molecules are subjected to high stress environments such as room temperature long term storage at high concentration levels, which are requirements for biological drug formulation. So to create molecules that can withstand such stressful environments while retaining their therapeutic properties, scientists need access to tools that can fully characterize and provide molecular functional insights for their molecules of interest. In this webinar, we will showcase  a new module in Discovery Studio dedicated to the identification of sites of aggregation using the experimentally validated Spatial Aggregation Propensity algorithm developed by Prof. Trout at MIT. In the webinar we will provide some examples of the type of analysis that we can now do with a long term goal of helping design better biological molecules.

In today’s fast-paced research environment, sharing and visualizing modeling results is an increasingly essential part of the discovery workflow.  Indeed, collaborating research teams can be geographically distant, adding to the challenge of effectively communicating key research findings.  With the latest release of Discovery Studio (DS), version 3.1, Accelrys has significantly updated it’s free accompanying visualization software, to fully support all the latest rendering and Storyboard enhancements in DS3.1.  In this webinar, learn how the latest release of our free 3D visualization plug-in, DS ActiveX Control can be leveraged to successfully share and communicate results

The latest release of Accelrys’ Discovery Studio 3.1 builds on the new release of Pipeline Pilot 8.5, providing enhanced scalability and job parallelization capabilities to modeling and simulation studies.  This webinar will provide an overview of the new functionality available in the latest release, including new market-leading tools to predict both the sites and propensity to aggregate in therapeutically important proteins.  Furthermore, we will also showcase enhancements to our free collaboration and visualization tools, further helping scientists to efficiently and effectively share key modeling results with research colleagues.

Recent advances in the GOLD docking program include a new scoring function, ChemPLP, and ensemble docking, which allows the user to efficiently dock against multiple models of the target protein, thus taking account of protein flexibility.

We will describe both these enhancements and present validation data showing how their use might benefit your bioactive discovery program.  We will also demonstrate how the Discovery Studio interface can be used to quickly and easily set up ensemble docking GOLD protocols and farm the jobs off into the cloud environment.

FieldStere from Cresset identifies novel bioisosteric analogues of ligands of interest, using field-based similarity of fragments. Through the Accelrys Partner Program, Pipeline Pilot protocols have been developed that allow set-up, execution and analysis of results from FieldStere calculations within Discovery Studio 3.0. We will show the use of this integration, and how Discovery Studio 3.0 can be used to add further value through seamless application of subsequent computational analysis on the initial result set.

GRID from Molecular Discovery has been applied in the field of structure-based drug design for over 25 years. Applications of GRID Molecular Interaction Fields range from physicochemical property prediction, virtual screening, ADME modeling, site of metabolism prediction, in addition to optimization of potency and selectivity through structure-based design or 3D QSAR techniques.  Through the Accelrys Partner Program, prototype Pipeline Pilot protocols have been developed that allow set-up, execution and analysis of results from GRID calculations within Discovery Studio 3.0. In this webinar we will discuss how and why GRID can aid your structure-based design program: the integration with Discovery Studio enables streamlined access to this science within a familiar interface, analysis of results within Discovery Studio offers potential for further value through integration with other tools and calculations.

The transfer of antigen binding loops from a non-human antibody donor to a human framework must be performed so that the native loop conformations are retained for binding. Often, antigen binding affinity is greatly reduced or abolished after CDR grafting. This binding activity is only restored after reverting one or more human framework residues to donor equivalents in the humanized antibody. The identification of critical framework residues that contribute to CDR conformation represents the most difficult and unpredictable step in the antibody humanization process. Here antibody modeling procedures and sequence analysis are described to assist the selection of framework mutations in the antibody humanization process.

Discovery Studio is built on Pipeline Pilot™ platform technology.  It is therefore  possible for scientists to access any computational codes  available in Discovery Studio at the Pipeline Pilot level. We will show through examples how scientists can customize or build their own protocols to automate tasks and meet precise needs.

A pharmacophore is a model which represents the key physico-chemical interactions, between a receptor target and ligand, that mediate biological activity. In DS 3.0 users can automatically create a series of pharmacophore models representing a receptor-ligand complex, and have these validated with known active and inactive compounds to determine the best pharmacophore for hit/lead identification.

One of the primary goals of protein design is to engineer optimized proteins by introducing mutations. Protein thermal stability is a key issue for chemical, biotechnology and pharmaceutical industries. We will present a new set of tools available in Discovery Studio 3.0 and  show how to calculate  mutation energies as well as  predict stabilizing mutations. Similarly, Protein-protein interactions are a key components of signal transduction. Methods for predicting  energetically important amino acids (interaction hot spots) at protein-protein interfaces are of increasing interest. We will present a new set of tools available in Discovery Studio 3.0   and show how to predict  computationally derived interaction hot spots. Computational results will be compared to experimental data on a set of selected examples.

The release of Accelrys’ Discovery Studio 3.0 in November extends our portfolio of small molecule drug design and market leading biological simulation tools and is focused on bringing new science from Accelrys and our partners, improved performance, and key enhancements to our users. This webinar will introduce users to key enhancements within the client designed to improve usability and encourage collaboration, as well as providing an overview of the new scientific developments.