Abstract
The accuracy of molecular dynamics (MD) simulations is limited by the availability of parameters for the molecular system of interest. In most force fields, parameters of common chemical groups are already present. With the development of novel small organic molecules as probes to study biological systems, more chemical groups require parameterization. An azide group is often used in studies of biological systems but computational studies are still impeded by the lack of parameters. In this paper, we present a set of molecular mechanics (MM) parameters for aromatic and aliphatic azido groups, and their application in MD simulations of a photoaffinity probe currently used in our laboratory for mapping binding modes available in the active site of histone deacetylases. The parameters were developed for the generalized Amber force field (GAFF) using density functional theory (DFT) calculations at B3LYP 6-311G(d) level. The parameters were validated by geometry optimization and MD simulations.
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Acknowledgments
We would like to thank Dr. Michael Brünsteiner for critical analysis of the manuscript. This study was funded in part by the Breast Cancer Congressionally Directed Research Program of Department of Defense Idea Award BC051554 and by the National Cancer Institute/NIH grant 1R01 CA131970-01A1. We also thank OpenEye Scientific Software for providing academic license for modeling software.
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Pieffet, G., Petukhov, P.A. Parameterization of aromatic azido groups: application as photoaffinity probes in molecular dynamics studies. J Mol Model 15, 1291–1297 (2009). https://doi.org/10.1007/s00894-009-0488-z
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DOI: https://doi.org/10.1007/s00894-009-0488-z