Homology Modeling: Generating Structural Models to Understand Protein Function and Mechanism

摘要: Geneticists and molecular cell biologists routinely uncover new proteins important in specific biological processes/pathways. However, either the functions or functional mechanisms of many these are unclear due to a lack knowledge their atomic structures. Yet, determining experimental structures presents technical challenges. The current methods for obtaining atomic-resolution biomolecules (X-ray crystallography NMR spectroscopy) require pure preparations at concentrations much higher than those which exist physiological environment. Additionally, has size limitations, with technology limited determination masses up 15 kDa. Due reasons, medically biologically do not exist. essential several purposes, including silico drug design [1], understanding effects disease mutations [2], designing experiments probe proteins. Comparative modeling gained importance as tool bridging gap between sequence structure space, allowing researchers build structural models that difficult crystallize by spectroscopy is tractable. modeling, homology exploits fact two whose sequences evolutionarily connected display similar features [3]. Thus, known protein (template) can be used generate model (query) notknown.