Tuesday, September 4 | 12:15-13:15
MOEsaic: The application of Matched Molecular Pair Analysis to SAR Exploration
Presenters: Andrew Henry & Alain Ajamian
With the increasing size of data sets and the parallel development of multiple structural series in medicinal chemistry projects, managing and analyzing structure activity/property relationship data is becoming ever more challenging. Tools and methods for the efficient visualization, analysis and profiling of compounds therefore remain of deep interest. Here, we describe a new web-based application, MOEsaic, which enhances typical medicinal chemistry workflows aimed at interrogating the SAR/SPR data through the application of interactive matched molecular pairs (MMP) analysis and R-group profiling.
1. What is MOEsaic?
2. How does MOEsaic identify matched molecular pairs?
3. Application areas for SAR exploration
MOEsaic workflow for profiling compounds and identifying activity cliffs using matched molecular pairs.
1. Description of MOEsaic interface
2. Structure alignment
3. Substructure searching
4. Applying property filters and plotting data
5. Matched molecular pair analysis
6. R-group fragmentation and profiling
Wednesday, September 5 | 12:15-13:15
Data Driven Drug Design – Using LiveDesign
Presenter: Nathaniel (Noj) Malcolm
LiveDesign is a novel platform delivering cheminformatics and expert computational models side by side in a highly collaborative and intuitive web-based tool. By presenting experimental data alongside predictive data and models, a broad range of scientists can drive new ideas by asking the key questions and easily exploring chemical space. We will show how this can be leveraged in a Hypothesis or Data Driven Design framework to optimize the Design/Test/Make cycle.
In this workshop we will introduce LiveDesign in the context of real-world medicinal chemistry workflows. This will range from rapid querying of the existing SAR, through to graphical exploration of experimental and predictive data to aid profiling and prioritization of new ideas. We will explore use of LiveDesign to capture compound progression tracking, from initial idea through synthesis and assay data analysis.
Embedded 3D docking and pharmacophore model visualization are key components of the LiveDesign platform and we will show how to make the most of this information. We will show easy use of validated Glide1 docking models in a selectivity study of COX1 and COX22. Finally attendees will be able to “Design a Drug” using the interactive docking tools, to propose selective COX2 inhibitor.
1. Friesner, R. A.; Murphy, R. B.; Repasky, M. P.; Frye, L. L.; Greenwood, J. R.; Halgren,T. A.; Sanschagrin, P. C.; Mainz, D. T., "Extra Precision Glide: Docking and Scoring Incorporating a Model of Hydrophobic Enclosure for Protein-Ligand Complexes" J. Med. Chem., 2006, 49, 6177–6196
2. Plount-Price, M. L.; Jorgensen W. L., “Analysis of Binding Affinities for Celecoxib Analogues with COX-1 and COX-2 from Combined Docking and Monte Carlo Simulations and Insight into the COX-2/COX-1 Selectivity” J. Am. Chem. Soc., 2000, 122 (39), pp 9455–9466