摘要
The polarized protein-specific charges （PPC） of human a-thrombin （thrombin） and its inhibitor （L86） are made possible by employing the recently developed molecular fractionation with conjugate caps approach incorporated the Poisson-Boltzmann model. Molecular dynamics （MD） simulations of thrombin have been carried out to investigate the dynamics and stability of the thrombin-inhibitor using PPC and AMBER charges respectively. Detailed analysis and comparison of MD results show that the PPC can correctly describe the polarized state of the thrombin and L86. Especially, the root-mean-square deviation of backbone atoms and the hydrogen bonds using PPC are more stable than the AMBER charge. The present results indicate that protein polarization plays critical roles in maintaining the compact structure of thrombin.
The polarized protein-specific charges （PPC） of human a-thrombin （thrombin） and its inhibitor （L86） are made possible by employing the recently developed molecular fractionation with conjugate caps approach incorporated the Poisson-Boltzmann model. Molecular dynamics （MD） simulations of thrombin have been carried out to investigate the dynamics and stability of the thrombin-inhibitor using PPC and AMBER charges respectively. Detailed analysis and comparison of MD results show that the PPC can correctly describe the polarized state of the thrombin and L86. Especially, the root-mean-square deviation of backbone atoms and the hydrogen bonds using PPC are more stable than the AMBER charge. The present results indicate that protein polarization plays critical roles in maintaining the compact structure of thrombin.
基金
Supported by the National Natural Science Foundation of China under Grant Nos 11147026, 21203224, 11274206 and 31200545, the Scientific Research Award Fund for the Excellent Middle-Aged and Young Scientists of Shandong Province under Grant No BS2011SW046, the Natural Science Foundation of Jiangsu Province under Grant No BK2012500, and the Postdoctoral Science Foundation of China （20110490163, 2012T50627） .
