THE CAMBRIDGE CRYSTALLOGRAPHIC DATA CENTRE (CCDC)

Transcription

1 ABOUT THE CAMBRIDGE CRYSTALLOGRAPHIC DATA CENTRE (CCDC) The CCDC is the trusted research institution responsible for the 50-year old Cambridge Structural Database (CSD) and its applications. Used by thousands of scientists in industry and academia, the CSD is essential to unlock knowledge and discovery potential from crystal structure data. CCDC SCIENTIFIC SESSIONS 249th American Chemical Society Annual Meeting & Exposition, Denver, Colorado, USA

2 Impact of crystal structures over the last, and next, 50 years Measuring the impact of scientific research is an important guide for fund distribution, individual researchers and those engaged in the communication of scientific output. Traditional metrics use journal article citations and impact scores; however there is increasing interest in alternative metrics that draw on other sources of data. How can scientific data repositories and databases help in understanding impact and what are the challenges associated with this? This presentation, timed to coincide with the 50th anniversary of the Cambridge Structural Database, will explore how we can measure the impact of 750,000 published crystal structures. We will soon be in receipt of 100,000 structures per year. How can we measure the impact of structures individually and as a whole? What mechanisms can we put in place to help better track the reuse of data? And to what degree should we be concerned about quality vs quantity? Suzanna Ward (CCDC) Date: Sunday, March 22, 2015 Time: 1:50pm - 2:15pm Abstract Symposium Name: Defining Value in Scholarly Communications; Evolving Ways of Evaluating Impact on Science Paper ID: Reporting and reuse of crystal structure data and knowledge For half a century the Cambridge Crystallographic Data Centre (CCDC) has provided services that facilitate the reporting and reuse of small molecule crystal structure data. In recent years, we have evolved in order to manage the deposition of almost 100,000 structures per year and respond to the changing demands and expectations around scientific communication. These changes build on CCDC's history of providing access to datasets that support claims made in the scientific literature and of providing software applications that unlock knowledge captured in around 750,000 crystal structures for reuse across chemistry domains. This presentation, timed to coincide with the 50 th anniversary of the Cambridge Structural Database, will describe recent developments specifically targeted at improving the validation, discoverability and reuse of crystal structure data and knowledge for current and future generations of researchers. Dr. Ian Bruno (CCDC) Date: Monday, March 23, 2015 Time: 3:45pm - 4:15pm Abstract Symposium Name: Research Results: Reproducibility, Reporting, Sharing & Plagiarism Paper ID: LIT-CCDC-TLS-001 v th American Chemical Society Annual Meeting, Denver Colorado, USA - March 22-25, 2015 Page 1 of 4

3 Insights into hydration propensity from systematic analyses of water in crystal structures Molecules love to crystallise with water. The adaptive hydrogen bonding networks we see in small molecule lattices are frequently a thing of beauty. However, the technical analysis of such networks can be daunting. It is also challenging to predict whether a molecule is likely to form a hydrate in the crystalline form and, if so, how stable such a form would be. We can also apply the analysis of hydration in small molecule lattices to protein-ligand systems. Many of the water patterns are common in macromolecular and small molecule systems and we are teased with the seductive possibility of using our knowledge derived from the water molecules placed in small molecule structures to help understand the affinity and solubility of drug molecules. This presentation, timed to coincide with the 50th anniversary of the Cambridge Structural Database will demonstrate how we can efficiently analyse hydrated structures and use this information in drug discovery and development. Dr Shyam Vyas (CCDC) Time: 9:30am - 10:00am Ballroom 4F Abstract Symposium Name: Computational Study of Water Paper ID: Insights into molecular similarity from crystal structures The output of every published crystal structure determination of a small organic molecule is available for all. Data from these experiments not only teaches us about the structure of molecules, it also informs us of their interactions. When crystallizing, a molecule creates its own most preferred environment. This has given us invaluable insights into molecular recognition. But a comparison of these environment allows us to do something more to compare molecules based on their interaction preferences. This presentation, timed to coincide with the 50th anniversary of the Cambridge Structural Database, will highlight how Full Interaction Maps describe the environment around a molecule in a lattice and can be used to compare molecules from the perspective of one molecule looking at another. We will also see how experimentally derived interaction fields can be used in virtual screening approaches. Time: 1:35pm - 2:00pm Abstract Symposium Name: Molecular & Structural 2D & 3D Chemical Fingerprinting: Computational Storing, Searching, & Comparing Molecular & Chemical Structures Paper ID: LIT-CCDC-TLS-001 v th American Chemical Society Annual Meeting, Denver Colorado, USA - March 22-25, 2015 Page 2 of 4

4 Using crystal structures to understand pharmaceutical materials Given the overwhelming proportion of small-molecule pharmaceutical therapies that are administered as crystalline solids, it should come as little surprise that the 750,000 crystal structures available to all can play a huge role in successfully developing the solid form of a compound, through the selection of the formulation with optimal physical properties. The geometrical insights and understanding of molecular interactions, from tens of millions of experimental observations allows us to build a probabilistic framework, in which we can understand the likely issues and opportunities presented to us for any molecule. This presentation, timed to coincide with the 50th anniversary of the Cambridge Structural Database, will outline how we can apply such a framework to determine the best strategy of taking a clinical candidate from molecule, to approved API. Dr Shyam Vyas (CCDC) Time: 2:00pm - 2:30pm Ballroom 1F Abstract Symposium Name: Materials Science Paper ID: Small molecule crystal structures in drug discovery and development The modern drug discovery scientist is bathed in structural information. Crystal structures of molecular targets can now be determined for almost every target class, often with ligands of interest. Many a drug discovery story tells of the involvement of structure-based drug design. But even more pervasive is the role of small molecule crystal structures. So much so, that the contribution of structural chemistry to drug discovery programs often goes unnoticed. This presentation, timed to coincide with the 50th anniversary of the Cambridge Structural Database will outline the immense contribution structural chemistry has made, and can make, to affinity optimisation, selectivity tuning, SAR determination, solubility enhancement, isostere selection, scaffold hopping, bioavailabilty, distribution and solid form optimisation. Time: 1:30pm - 2:00pm Ballroom 4E Abstract Symposium Name: Drug Discovery: Ligand-Based Paper ID: LIT-CCDC-TLS-001 v th American Chemical Society Annual Meeting, Denver Colorado, USA - March 22-25, 2015 Page 3 of 4

5 Communicating crystal structures: Successes, challenges, and opportunities The Crystallographic Framework (CIF) has had a transformative effect on the communication and publication of crystal structure determinations since the crystallographic community widely adopted it in the 1990s. CIF combines both data and textual information relating to an experiment and has enabled streamlined workflows for validation, publishing and archive of crystal structure determinations. This presentation, timed to coincide with the 50th anniversary of the Cambridge Structural Database, will reflect on reasons for the successful adoption of CIF, future opportunities for building on the framework and lessons that may be applicable to the communication of data from other domains. It will also describe the benefits and challenges of linking the results of a crystal structure determination to a reliable representation of the chemical substance studied. Dr. Ian Bruno (CCDC) Time: 3:20pm 3:50pm Abstract Symposium Name: Development & Use of Data Format Standards for Cheminformatics Paper ID: Experimentally derived interaction fields as a basis for ligand-based virtual screening The crystal structures of molecules tell us much more than their geometry they tell us about their interactions with each other. Small molecule crystals are a superb surrogate for protein-ligand complexes, which simply contain a subset of the chemical functionality we see in small molecule crystal lattices. Our understanding of the preferred interactions of small molecules has supported the development of a molecular optimisation framework, which we can apply to many problems in drug discovery. One such problem the need to overlay molecules in a biologically relevant manner and identify molecules with the potential for similar interactions will be addressed. In addition, this presentation, timed to coincide with the 50th anniversary of the Cambridge Structural Database will show how the experimentally determined interaction fields of molecules can be used in virtual screening approaches. Time: 3:30pm - 4:00pm Ballroom 4E Abstract Symposium Name: Drug Discovery: Ligand-Based Paper ID: LIT-CCDC-TLS-001 v th American Chemical Society Annual Meeting, Denver Colorado, USA - March 22-25, 2015 Page 4 of 4