Vibrational behavior analysis of the complex of HIV-1 protease with inhibitor

Abstract

For elucidation on the structure and function of protein-ligand complex, it is important to understand both the kinetical and thermodynamical behavior in biological environment. Especially, temperature dependency on their biological activity reveals that the thermal fluctuation plays an important role on the dynamic interaction between protein and ligand. In this study, we propose a new conformational analysis approach to understanding protein-ligand complex functions. Practical mixing of calculated protein-ligand complex by thermodynamic normal mode analysis gives an important technique for finding many plausible structures of protein-ligand complex. Base on this vibrational simulation, the difference of dynamical behaviors between HIV-1 protease and the complex with inhibitor in water will be discussed. As a result, in only protease system, Gly49 fluctuates with neighbor residues. In protease-ligand complexed system and protease-ligand in crystal waters, Gly49 does not fluctuate. Asp25 and Asp25', which are active site, are motionless in any systems. Therefore, I concluded this vibration in this mode is related to activity between protease and inhibitor.