Dynamical correlation in proteins

• Main Authors: Shian-Lei Ho, 何仙蕾
• Other Authors: Jenn-Kang Hwang
• Format: Others
• Language: en_US
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/47874162911489211925

碩士 === 國立交通大學 === 生物科技系所 === 96 === There are residues in proteins not directly bind to ligand, but they can dramatically affect the binding affinity(tenfold or higher)between protein and ligand. These residues called hot spot residues which can be detected by alanine scanning mutagenesis in protein interface. For the purpose to design experiment effectively, we develop some methods to find the geometric correlation between binding sites and hot spot residues.These methods can identify hot spot residues and non-hot spot residues. The molecular dynamics(MD) simulations with complex molecular potential energy can analize the motion of proteins. MD simulation is a powerful tool, but it is time-consuming. For this reason, we use simplified mechanical methods such as Gaussian network model(GNM), and our methods, centroid model(CM) and weighted contact-number model(WCN) to discuss the dynamical correlation in proteins. Howerer, the cross-correlation matrix in GNM can not identify the hot spot residues. The improved WCN and normalized centroid model can identify these hot spots. The methods we developed can show that there are high correlation between functional hot spot residues and binding sites in geometrical relation. In the end, we can also find the high spatial correlation between binding sites and highly sequence conserved residues.