標題: 利用分子動力模擬找出蛋白質序列演化之可能路徑--肌紅蛋白為例
The identification of possible protein evolutionary pathways via molecular dynamic simulation -- using myoglobin as the example
作者: 蔡宗翰
Tsai, Tsung-Han
林勇欣
Lin, Yeong-Shin
生物科技學系
關鍵字: 分子動力模擬;肌紅蛋白;蛋白質演化;molecular dynamic simulation;myoglobin;protein evolution
公開日期: 2010
摘要: 以分子動力學(molecular dynamics;MD)來模擬研究蛋白質序列演化,可以從模擬中快速且迅速的了解蛋白質演化突變後可能發生的結構與穩定性的變化。在現今強大的電腦運算資源下,此方法除了能節省不少實驗所須之高額成本,更可以節省不少時間。我們首先選定了以肌紅蛋白(myoglobin)做為第一個標的蛋白。肌紅蛋白為一種血基質蛋白(heme-protein),在脊椎動物體內具有儲存及攜帶氧氣的功能。肌紅蛋白為第一個利用X-ray 結晶學解出結構的蛋白質,在結構學上已經被研究了相當多年,具有許多完整的結晶結構與相關的實驗數據,非常適合做蛋白質演化的研究. 本研究利用軟體將已知之鯨魚肌紅蛋白(1MBO)做單點或多點突變,經分子動力學模擬後,找尋方法判斷其結構是否穩定,然後探討肌紅蛋白在分子演化上可能的演化路徑.在文獻資料中可以知道,肌紅蛋白在其HEME週圍的胺基酸具有保守性,且特定胺基酸和HEME的距離遠近與是否能幫助HEME穩定結合氧氣有很大關係.且發現HEME周圍有四個孔洞(cavities)可協助肌紅蛋白運送與儲存氧氣的功能,此四個孔洞周圍的胺基酸也是具有保守性。孔洞周圍的胺基酸距離影響孔洞的體積,也與是否維持正常的儲存與運送氧氣功能有關.我們的研究裡,利用這些具有保守性的胺基酸,在HEME周圍的與Fe測距離,而在孔洞周圍則兩者之間測距離。利用原生種(wild type)的分子模擬(MD)先過濾出具有相同距離範圍的配對,再利用這些配對來過濾突變之肌紅蛋白是否穩定的可能性並加以探討。
Using molecular dynamics simulation to unsterstand protein sequence evolution and understand the evolution of mutation which about the protein structure and stability. In today's powerful computing resources, this method can reduce the high cost of experiments and can also save a lot of time. We first selected to myoglobin as the first target protein at first. Myoglobin as a heme protein (heme-protein), in the vertebrate body with storage and carrying oxygen functions. Myoglobin is the first using X-ray crystallography the structure of the protein solution. The structure has been studied in the school q for many years, with much complete crystalline structure and the relevant experimental data. It is very suitable for the study of protein evolution. In this research, We use the software to mutant the whale myoglobin (1MBO) to do single or multiple point mutations. After molecular dynamics (molecular dynamics; MD) simulations, we will to find ways to determine the stability of its structure, and try to explore ie myoglobin protein sequence evolution on the possible evolutionary path. In the literature ,we can know, myoglobin have the conserved amino acids around the heme , and it can help the heme binding O2 with the distance from specific amino acids to HEME. It is also found that the four cavities around HEME can help myoglobin to transport and storage oxygen. The amino acids around this four holes are conserved. The surrounding amino acids pair distance may impact on the size of cavities and the normal function of the oxygen storage. In our research, we use of these conserved amino acids, and Fe in the HEME to measured the distance pair around HEME, and the amino acids distance pairs around the cavities .At first,we use of native species (wild type) molecular modeling (MD) to filter out the Distance pair with the same distance, and then we use these distance pairs to filter the myoglobin mutant if it is stable or not.
URI: http://140.113.39.130/cdrfb3/record/nctu/#GT079528516
http://hdl.handle.net/11536/41261
Appears in Collections:Thesis