Validation of hypothesis of pressure reversal mechanisms: 'Anesthetic binds to site, and squeezed out by pressure'

摘要

Pressure reversal hypothesis, "Anaesthetic binds to protein and increases the system volume, and will be squeezed out due to pressure" is proposed based on thermodynamics [1]. Lysozyme (Lyz) is known as a hydrolytic enzyme, and binds to anaesthetic, xenon. Binding coordinates of xenon is determined by X-ray structure analysis [2], In 2003, Lyz structure in solution at 2 kbar became obvious by high pressure NMR [3], Using these structures of Lyz at 2 kbar and 30 bar, we inferred that action site model of the hypothesis could be found from proper prediction of xenon binding site, and its energy at normal and high pressures. Xenon binding sites are known in Lyz, cleft site at substrate binding site and internal site located inside of cavity and were used for docking simulation, computer simulation to predict the structure and binding energy. The aim of this study is to find molecular model of pressure reversal hypothesis using docking simulation at high pressure.