An Attempt of Seeking Favorable Binding Free Energy Prediction Schemes Considering the Entropic Effect on Fis-DNA Binding

• DOI: 10.1021/acs.jpcb.2c07811
• Publication Date: 2023-02-03T20:30:12Z
• Authors: Song Luo; Danyang Xiong; Xiaoyu Zhao; Lili Duan
• Keywords: DNA binding site

Protein–DNA binding mechanisms in a complex manner are essential for understanding many biological processes. Over the past decades, numerous experiments and calculations have analyzed specificity of protein–DNA binding. However, accuracy free energy prediction multi-base DNA systems still needs to be improved. Fis is DNA-binding protein that regulates various transcription recombination reactions. In present work, we tested several methods predict based on this system find favorable scheme explore mechanism DNA. Two solvent models (explicit implicit models) were chosen dynamics process, predicted was more accurate under explicit model. When different Poisson–Boltzmann/Generalized Born (PB/GB) force fields (BSC1 OL15), it found by selected OL15 field performed better correlation between experimental values improved with increasing interior dielectric constant (Dk). Finally, using Dk = 8, GBOBC1 model combined interaction entropy (IE), which calculated entropic contribution (GBOBC1_IE_8), screened out analysis Fis–DNA system, validity method further verified testing Cren7–DNA system. By performing conformational minor groove, mutation central sequence A/T C/G deletion guanine 2-amino group would change groove width thus affect formation major altering atomic contact changing affinity Hopefully, series tests work can shed some light related studies systems.