The Modeling of Small Molecules and DNA Intermediates

1. + R L (1 or RL The Modeling of Small Molecules and DNA Intermediates Gabriel Vahi Ferguson, Marc Rideout, Anca Segall, Peter Salamon Department of Biomathematics, San Diego State University, San Diego, CA, USA Six Models Introduction Conclusions The Segall lab has previously identified peptides that have antibacterial activity at least in part because they interfere with DNA repair processes. Holliday junctions (HJ) are intermediates in DNA repair. A new small molecule, 1609-10, has been shown to bind to the HJs. To model the interaction, we are considering several mechanisms of 1609-10 (Ligand, L) binding to the HJ (Receptor, R). Each mechanism gives a set of equilibrium constants, and the goodness of fit between modeled and actual data will suggest which is the most likely mechanism of binding. Low sum of squared error suggest a reasonable fit; however based on AIC we believe model E represents the best fit out of the mechanisms considered. attaches. Models (right) describe the possible mechanisms of binding between the receptor and one or two ligands. Simplified mechanism k=number of constants n=number of data points SSE=sum of squared error 2AP location Each mechanism was expressed as a system of differential equations. After using Maple to combine the equations, the equation for the predicted fraction of complex is obtained and MATLAB’s “fminsearch” is used to find the best-fitting constants. Future Directions -Model multiple sites of binding to the HJ -Model peptide inhibitors using the same strategy This research was funded in part by the NSF 0827278 UBM Interdisciplinary Training in Biology and Mathematics grant to AMS and PS.