Accelrys Life Sciences Symposium

Events

Abstracts

Presenter: Francine Acher, Research Director, CNRS
Presentation Title: Molecular determinants of agonist selectivity in glutamate-gated chloride channels

Abstract: Rapid synaptic transmission in the nervous system is mediated by a very large and diverse family of ligand-gated ion channels (LGICs). One major group of LGICs are of pentameric structure, and are characterized by a highly conserved cysteine loop that is found in the extracellular N-terminal domain. These have been named "cys-loop receptors". They are activated by many different neurotransmitters such as Ach, GABA, glycine, serotonin, glutamate, histamine and dopamine. Some of these LGICs contain an additional cys-loop in the N-terminal domain. These 2-cys loop LGICs are anionic. The glycine receptor is the best known example of the 2-cys loop receptors, and the only vertebrate one. Two invertebrate 2-cys loop glutamate-gated chloride channels (GluClR's) from nematodes and arthropods (Aplysia) have been characterized. The former is only gated by glutamate whereas the latter may also be activated by GABA, b-alanine and taurine.
The recent crystallization of the GluClR from C. elegans revealed the binding pocket of the nematode receptor. An alignment of the protein sequences of the nematode and molluscan GluClR's showed that the Aplysia receptor does not contain all of the residues defining the binding mode of the nematode receptor. We built a homology model of the Aplysia receptor docked with glutamate. The comparison with the nematode X-ray structure and site directed mutagenesis investigations revealed a set of residues that determines the GluClR selectivity. These results add to the gating mechanism that was recently proposed by Calimet et al .


Presenter: Sudharsan Sridharan, Ph.D., MedImmune, Cambridge, UK
Presentation Title: Application of computational structural biology tools in biotherapeutic drug discovery.

Abstract: The biotherapeutics drug industry faces many challenges during the discovery and development stages. The use of computational structural biology and structural bioinformatics tools is gaining momentum in solving some of these challenges. In this presentation case studies of how MedImmune  applies  cutting-edge computational tools such as those for protein-protein docking, prediction of aggregation prone regions and in silico mutagenesis available in the Accelrys Discovery Studio software will be discussed. Further advancements in such computational tools needed by the biotherapeutics industry to fully benefit from protein structural data will also be highlighted.


Presenter: Leo-Van Buren, Scientist, Unilever
Presentation Title: Structure activity relationship studies on the bitterness of flavonoids and related compounds

Abstract: Flavonoids are chemically diverse plant components which are often associated with a positive health effect but, depending on their concentration, are known to contribute to the bitter taste of many foods. In order to increase product acceptance by consumers, strategies for removing or masking bitterness are therefore useful for the food industry.

At Unilever we have developed 2D-fingerprint and 3D-pharmacophore models in the Pipeline Pilot and Discovery Studio software from Accelrys. These models were used to determine the relationship between molecular descriptors and measured bitter receptor activation. These models have resulted in the discovery of several novel actives and bitter blocking compounds. This work has been carried out in close collaboration with the laboratory of Food Chemistry at Wageningen University.


Presenter: Jérémy Besnard, Chief Technology Officer, Ex Scientia
Presentation Title: De novo design of polypharmacological compounds in the Cloud – bringing expertise together without geographical barriers

Abstract: We have developed an evolutionary algorithm that generates virtual compounds that fulfil desired multi target objectives through iterative steps and different modelling mechanics. On our first experience we succeeded in generating novel, drug-like compounds with activities against multiple GPCRs (doi:10.1038/nature11691), but also against different gene families.
The original algorithm used Bayesian models built using the ChEMBL database of bioactivity and was entirely built using Pipeline Pilot components and Pilot scripts. It was then extended to include modules from Discovery Studio and OpenEye to provide 3D information; as well as mining client and proprietary databases.
To share the process through our company and to provide a robust and secure IT solution we integrated the different software and databases into Amazon cloud (AWS).
The presentation will describe the algorithm and its successes and how we integrated it into the cloud to allow different expertise to be joined together even when people of the company are scattered around UK and in the US (chemoinformatics, bioinformatics and medicinal chemistry).


Presenter: Luc Spitzer, IT Data Manager, Inventiva
Presentation Title: Gemsight – Integration of Accelrys Insight into Inventiva

Abstract: Inventiva SAS is a drug discovery company dealing with multiple clients and projects. In order to meet our current needs, ensure flexible and stable reporting to clients, we enhanced our reporting portfolio by migrating to Accelrys Insight. One of the major criteria for selecting Insight is that it allows us to leverage on the powerful capabilities present in the underlying Pipeline Pilot tool set. We focused our development efforts in order to deliver both a stable project reporting tool and still provide an easy-to-use and flexible tool for scientist’s daily tasks such as:

  • Flexible display and mining of dose-response curves
  • SAR analysis
  • Data separation and access based on project/partner
  • Easy report generation for standard project reporting and customer-designed dedicated reports
  • Stable export of data to be shared with customers

Presenter: Jeroen Coppieters, Enterprise Architect, GSK
Presentation Title: BioRegistration at GSK -- a journey and strategic cornerstone
Abstract: GSK traditionally focused on small molecules and this was reflected in our R&D processes, IT systems and investments. Like many other large pharma , GSK Pharma Research and Development are shifting to large molecules because of significant benefit for patients. At the same time, regulatory requirements for identification of pharmaceutical products are increasing. We have existing biological inventory systems for handling reagents but these are not suitable for recent advances in biological sciences which are generating high volumes of novel biological samples. Following a strategic review of our discovery software we started a project to introduce the registration of biologics and to integrate this with our existing infra-structure which handles small molecule registration. 


Presenter: Rob Brown, Senior Director of Life Sciences Marketing, BIOVIA
Presentation title: BIOVIA Informatics Strategy and Roadmap

Abstract: Significant changes have occurred in the last few years in Life Sciences Research including the move to a balanced portfolio between biologics and small molecules, as well as the increase in collaborative research across multiple companies, CROs and academic institutions. At the same time significant changes have been occurring in the technology landscape with the increased importance of cloud computing, mobility, social collaboration and the application of big data analytics.
Accelrys has developed a new informatics suite harnessing these new technologies to address the new kinds of research challenge. In this talk we will discuss the strategy that we have developed, describe the current informatics suite and provide a roadmap for our future development. Products covered in this talk will include Accelrys Insight, Accelrys Chemical and Biological Registration, Accelrys Electronic Notebook and Accelrys Notebook, ScienceCloud and Accelrys Pipeline Pilot.


Presenter: Craig Tulig, Director, Research Informatics, Takeda Pharmaceuticals
Presentation title: Changing the Engine while flying the Airplane: New Systems and New Science in Oncology Research

Abstract: Although the research site of Takeda Pharmaceuticals International Co. could be considered young on the timescale of Pharmaceutical companies, many of its key drug discovery systems were facing end-of-life, while at the same time trends in the practice of oncology research were driving the needs for new research systems.  Biotherapeutics research calls for classes of systems with a fundamental understanding of relationships in biology not typically found in systems supporting small molecule research.  Small molecule researchers in oncology increasingly look to combine novel compounds with standards of care or even consider novel-novel combinations, all of which require new ways of thinking about compound activity and efficacy.  This talk will review our unified approach to replacing aging software systems while at the same time deploying new capabilities to support research initiatives.


 

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