Padrón-García J Alexander, Crespo-Otero Rachel, Hernández-Rodríguez Erix William, Garriga Pere, Montero Luis A, García-Piñeiro José Carlos
Laboratorio de Química Computacional y Teórica, Facultad de Química, Universidad de la Habana, Havana, Cuba.
Proteins. 2004 Nov 1;57(2):392-9. doi: 10.1002/prot.20204.
Changes induced by mutations in rhodopsin that are associated with the degenerative visual disease retinitis pigmentosa result in an altered pattern of light absorption according to quantum mechanical simulations and reference experimental works. Eleven single-point mutations associated with retinitis pigmentosa at and in the proximity to the retinal binding pocket of rhodopsin have been modeled in silico and their spectra calculated with the NDOL (Neglect of Differential Overlap accounting L azimuthal quantum number) a priori method. The altered pattern of absorption found would lead to cumulative consequences in energy dissipation with aging. Different energy balances in the case of mutants at the very molecular level, compared to native nonmutated rhodopsin, can cause permanent cellular stress and would play a role in the progression of the retine degenerative process. It could explain the worsening of the pathological condition mostly in adults and suggests the probable beneficial effects of using quenching drugs and protection devices against excess of light in the early stages of life for avoiding or reducing potential damage.
根据量子力学模拟和参考实验研究，视紫红质中与退行性视觉疾病视网膜色素变性相关的突变所引起的变化，会导致光吸收模式发生改变。已通过计算机模拟对视紫红质视网膜结合口袋及其附近与视网膜色素变性相关的11个单点突变进行了建模，并使用NDOL（考虑方位角量子数的忽略微分重叠）先验方法计算了它们的光谱。所发现的吸收模式改变会随着年龄增长在能量耗散方面产生累积后果。与天然未突变的视紫红质相比，突变体在分子水平上的不同能量平衡会导致永久性细胞应激，并在视网膜退行性过程的进展中起作用。这可以解释为什么病理状况大多在成年人中恶化，并表明在生命早期使用猝灭药物和防强光保护装置可能具有有益效果，以避免或减少潜在损害。
