Standard reference simulations for docking and scoring: Enabling robust computational screening for drug design

COMP 196

A. Jayne Oliver-Kapur, jaynekapur@gmail.com, Computational Chemistry Group, National Institute of Standards and Technology, 100 Bureau Drive, Stop 8380, Gaithersburg, MD 20899-8380, Anne M. Chaka, Physical and Chemical Properties Division, National Institute of Standards and Technology, 100 Bureau Drive, Stop 8380, Gaithersburg, MD 20899-8380, Michael K. Gilson, Center for Advanced Research in Biotechnology, University of Maryland Biotechnology Institute, 9600 Gudelsky Drive, Rockville, MD 20850, and Frederick P Schwarz, frederick.schwarz@nist.gov, National Institute of Standards and Technology, 100 Bureau Drive, Stop 8310, Gaithersburg, MD MD 20899-838.
Our aim at the National Institute for Standards and Technology is to develop and evaluate a series of Standard Reference Simulations (SRS) to calculate ligand-receptor binding energies, assess the accuracy of the range of methods currently available, and the uncertainty introduced by assumptions and simplifications. Such a dataset will be helpful in the discovery/development of lead compounds within the pharmaceutical industry.

For this work we have selected a small, well-defined cyclodextrin host and a test set of diverse guest ligands as our model system. We aim to demonstrate the concept of a SRS to calculate free energies of binding by utilizing a range of computational methods from classical pair potentials to ab initio dynamics calculations with forces calculated from quantum mechanics on the fly. Additionally experimental binding data obtained by ITC/Biacore will be provided for direct comparison to these computational data. Here we present the results of our preliminary calculations

 

Poster Session -- Sponsored by Novartis Institutes for BioMedical Research
6:00 PM-8:00 PM, Tuesday, 30 August 2005 Washington DC Convention Center -- Hall A, Poster

Sci-Mix
8:00 PM-10:00 PM, Monday, 29 August 2005 Washington DC Convention Center -- Hall A, Sci-Mix

Division of Computers in Chemistry

The 230th ACS National Meeting, in Washington, DC, Aug 28-Sept 1, 2005