Development and refinement of a coarse grained model for the dynamic representation of chromatin

Abstract

This project contributes to the development of a coarse-grained model at the MMB lab at IRB, designed to capture the sequence-dependent dynamics of DNA and its interactions with proteins using simplified Hamiltonians derived from atomistic potentials. A key objective was to assess its ability to reproduce the sequence-specific binding of transcription factors (TFs). To this end, a semi-stochastic algorithm was implemented to generate physically realistic initial configurations. Additionally, Free Energy Perturbation simulations were performed to quantify the impact of single-base mutations on TF binding affinity. Results highlight the differential energetic contribution of individual bases to protein-DNA interactions