Role of Conformational Changes in DNA Recognition in Transcription Factors having Helix-Turn-Helix Motif

Abstract

DNA-binding proteins play a crucial role in various cellular processes, some of these have a unique structural arrangement, the helix-turn-helix motif, which enables them to bind to DNA molecules in a specific manner. Upon binding to DNA, conformational changes occur in both the protein structure and the DNA molecule, making it essential to quantify and characterise these changes. This work aims to quantify and characterise the conformational changes in the protein structures. This is achieved by calculating the root-mean-square deviation of the protein structure in the free state and DNA bound state. A database is curated which has a significant number of DNA-bound and unbound pairs available. For the unbound structure of the proteins, pre-processing is required to remove chains other than those found in its corresponding DNA-bound structure followed by superimposing it to the DNA-bound structures obtained from the Protein Data Bank (PDB) to calculate the RMSD. After quantifying the conformational changes using RMSD values, the proteins are categorised into six types based on their observed conformational changes. In this study, the primary objective is to conduct a comprehensive analysis of conformational changes in DNA-binding proteins and investigate their correlation with various protein properties. By exploring these correlations, the study aims to unravel potential patterns or dependencies between the extent of conformational changes and the diverse properties of DNA-binding proteins. Such insights can shed light on the functional implications of structural variations in DNA-protein interactions, providing valuable information about how protein dynamics contribute to DNA recognition and binding. In addition, this work endeavours to broaden its scope by attempting to replicate DNA-bound complexes through the utilisation of freely available structures. By doing so, it aims to assess the reliability and accuracy of docking methods in predicting and reconstructing these complexes. The primary objective is to evaluate the feasibility and effectiveness of such techniques in the context of complex formation between DNA and protein molecules.