Invest ten minutes to obtain 3D-QSAR based structure/activity insight and predictions!
In the Tripos booth at the upcoming Chicago ACS meeting, you can try out the new topomer CoMFA methodology. On your own structure-activity data set, if you can bring one (and we hope you will!), or one of ours. Our experience with over 20 datasets suggests that, in less than half an hour, you will be able to create the familiar contour plots and make predictions for other structures. Our goal is to gain broad experience with real users and real data sets before the initial release of what appears to be a very useful capability. So, there will always be a usability expert and a discovery-experienced scientist present as you try out topCoMFA, and of course I will also be around as much as possible. We will be collecting information on your impressions of the user interface and your overall experience, and, if enough of you can bring data sets, there may be a chance to generate meaningful ’success rates’ on real-world problems.
The essence of topomer CoMFA is a surprisingly effective ‘automatic alignment’ procedure. Each structure is broken into two fragments, either by clipping R groups off a structurally constant core or by cutting a single acyclic bond. The only input required from you is guidance in systematically identifying the fragmentation bonds. Topomer generation and PLS analysis are then entirely automatic. If the resulting CoMFA model is satisfactory (the usual outcome), graph display and prediction are one-button operations. A new possibility with topCoMFA’s 3D-QSAR models is to search your corporate compound registry for fragments promising beneficial effects, although that capability will probably not be made available at the booth.
The only data needed for topomer CoMFA are the structures (nothing except for connectivities) with their measured activities (our experience is all with pI or log values but we can handle other forms). The data format can be SLN, .sdf, smiles, or .mol2. It will be more convenient if training and test (prediction) sets are provided in separate files. The medium might be a CD or email attachment to Brian Masek and/or me. We will of course take all practicable precautions to safeguard the IP that your data may represent, for example immediate deletion of your data from our computer at the end of your trial. Hour-long time slots are planned on Monday and Tuesday from 9 AM until 2 PM. To schedule one, please contact Diana O’Rourke.
Topomer CoMFA is one of several topomer-based technologies created over the last decade, originally for the exclusive support of synthetic efforts at Tripos Discovery Research in Bude, UK, and now being commercially developed within a new ‘technology preview’ program that is generally intended to make such new technologies more immediately productive in use.
For more about topomer CoMFA, please see: Cramer, R. D. Topomer CoMFA: A Design Methodology for Rapid Lead Optimization, J. Med. Chem., 2003, 46, 374-389.
Dick Cramer
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