| 학회 | 한국고분자학회 |
| 학술대회 | 2005년 가을 (10/13 ~ 10/14, 제주 ICC) |
| 권호 | 30권 2호 |
| 발표분야 | 고분자 구조 및 물성 |
| 제목 | Electrostatic energy calculation on pH-induced conformational change of influenza virus hemagglutinin |
| 초록 | The destabilization of native hemagglutinin upon pH decrease is investigated in order to elucidate the origin of pH-induced conformational change of influenza virus hemagglutinin. The change of conformational energy and solvation energy upon pH change is calculated for the whole structure of native hemagglutinin, i.e. the receptor binding domain (HA1) and the fusion domain (HA2). First, the ionization states of all ionizable residues in the native hemagglutinin are determined under pH5 and pH7 conditions by using the finite difference Poisson-Boltzmann method and a Monte Carlo sampling method. From the charge distributions of native hemagglutinin at pH5 and pH7, the difference of conformational energy between pH5 and pH7 is calculated by using the CHARMM22 force field. Then, the difference of solvation energy between pH5 and pH7 is also calculated by using the finite difference Poisson-Boltzmann method. The calculations reveal that the conformational energy of native hemagglutinin is higher at pH5 than at pH7, whereas the difference of solvation energy between pH5 and pH7 is not significant. Consequently, as pH decreases from 7 to 5, the native hemagglutinin is destabilized mainly due to unfavorable charge-charge interaction between ionizable residues of native hemagglutinin at lower pH. Therefore, it is conjectured that the low pH-induced conformational change of hemagglutinin from native state to fusogenic state which occurs when pH drops from 7 to 5 in endosome can be initiated in order to relieve the unfavorable interaction in native hemagglutinin. The same calculation is performed at pH5 for the fusion domain of fusogenic state of hemagglutinin and the result is compared with that of the fusion domain of native hemagglutinin. As a result, it is further confirmed that the fusogenic state of hemagglutinin has a lower conformational energy at pH5 than that of native state of hemagglutinin. Fig. 1. Crystal structures of influenza virus hemagglutinin: (a) native state and (b) fusogenic state. Negatively charged residues and positively charged residues are represented as blue and red spheres, respectively. |
| 저자 | 최호섭, 허준, 조원호 |
| 소속 | 서울대 |
| 키워드 | influenza virus; hemagglutinin; finite difference poisson-boltzmann method |
