Protein dynamics and contact topology studies reveal characteristics of Protein-DNA binding and distribution of enzyme catalytic sites

蛋白質的接觸拓樸和動力學研究揭露蛋白-DNA接合特徵及酵素活性中心的分佈偏好

艾拉文(Aravind Chandrasekaran)

指導教授 ： 楊立威

國立清華大學/生命科學院/生物資訊與結構生物研究所/碩士(2014年)

摘要

Effects of protein dynamics on protein-DNA binding have not been analyzed thoroughly so far. Using GNM and ANM, we well predict conformational change between DNA-free/DNA-bound forms. However, we fail to find fluctuation-magnitude-based characteristics to predict DNA binding sites. GNM-based Domain-planes (D-planes) derived from the unbound proteins are used to determine significant DNA-binding orientations with the results that larger than 95% of the 110 DNA molecules being dissected through by these planes. In addition, we also report that enzyme active sites are close to the D-planes such that 90% of the studied 732 active sites are located within 50% rank from the D-planes. We compare and contrast the thermodynamic aspects of ligand-protein and DNA-protein binding. This study suggests potential applications for filtering out unlikely DNA-protein docking poses obtained from docking software.

關鍵字

彈性網絡模型 ； 構型變化 ； DNA結合蛋白質 ； DNA結合蛋白質結合位點 ； 預測酵素活性位置

並列摘要

Effects of protein dynamics on protein-DNA binding have not been analyzed thoroughly so far. Using GNM and ANM, we well predict conformational change between DNA-free/DNA-bound forms. However, we fail to find fluctuation-magnitude-based characteristics to predict DNA binding sites. GNM-based Domain-planes (D-planes) derived from the unbound proteins are used to determine significant DNA-binding orientations with the results that larger than 95% of the 110 DNA molecules being dissected through by these planes. In addition, we also report that enzyme active sites are close to the D-planes such that 90% of the studied 732 active sites are located within 50% rank from the D-planes. We compare and contrast the thermodynamic aspects of ligand-protein and DNA-protein binding. This study suggests potential applications for filtering out unlikely DNA-protein docking poses obtained from docking software.

並列關鍵字

ENM ； Conformational change ； protein-DNA binding ； protein-DNA binding site ； Enzyme active site prediction

參考文獻

Atilgan, a R. et al. (2001) Anisotropy of fluctuation dynamics of proteins with an elastic network model. Biophys. J., 80, 505–15.

Bahar,I. et al. (1998) Correlation between native-state hydrogen exchange and cooperative residue fluctuations from a simple model. Biochemistry, 37, 1067–75.

Bahar,I. et al. (1997) Direct evaluation of thermal fluctuations in proteins using a single-parameter harmonic potential. Fold. Des., 2, 173–81.

Bahar,I. et al. (2010) Global dynamics of proteins: bridging between structure and function. Annu. Rev. Biophys., 39, 23–42.

Bairoch,A. (2000) The ENZYME database in 2000. Nucleic Acids Res., 28, 304–305.