Poster Presentation 2014 International Biophysics Congress

P { margin-bottom: 0.08in; } Spontaneous conformational change of human angiotensin-I converting enzyme (ACE) studied by molecular dynamics simulations (#505)

Myunggi Yi 1 2 , Thi Tuong Vy Phan 1 2
  1. Pukyong National University, Busan, South Korea
  2. Center for Marine-Integrated Biomedical Technology, Busan, Korea

Hypertension, or high blood pressure, is a serious condition that can lead to coronary heart disease, heart failure, stroke, kidney failure, and other health problems. Angiotensin-I converting enzyme (ACE) plays an important role in regulating blood pressure of renin-angiotensin system (RAS). Understanding of structure and its conformational change, or dynamics, of ACE may provide information for design of more effective hypertension treatments. We carried out molecular dynamics (MD) simulations of ACE with and without ligands. In the ligand bound forms, we used two kinds of inhibitors. One is angiotensin II, the product of the enzyme function, and the other is bradykinin potentiating peptide b. We have observed that spontaneous conformational changes of ACE : wide-open, semi-open and closed forms of conformations. The unbound ACE fluctuates between semi-open and wide-open conformations required to accept angiotensin-I, the substrate, and to release angiotensin-II, the product. In the present of inhibitors, the conformations of ACE were influenced by the inhibitors, and ACE mainly stayed in the closed and semi-open conformations. The conformational flexibility and dynamics is required for the enzyme activity of ACE. This study indicates the importance of the structure as well as its conformational change and dynamics in order to understand complete functions of a protein.