Biopolym. Cell. 2002; 18(2):117-123.
Конформаційні зміни в структурі ВІЛ-1 протеази: дослідження методом молекулярної динаміки в піко- та наносекундному часових проміжках
1Ковальський Д. Б., 1Корнелюк О. І.
  1. Інститут молекулярної біології і генетики НАН України
    Вул. Академіка Заболотного, 150, Київ, Україна, 03680

Abstract

ВІЛ-1 протеаза є однією з найпривабливіших моделей для дизайну лікарських засобів у терапії СНІДу. Для потрапляння субстрату до активного центра протеази необхідно, щоб дві β-шпильки («флепи»), які його покривають, відкрилися на достатню для цього відстань. Саме тому «флепи» відіграють ключову роль у функціонуванні ВІЛ-1 протеази. Незважаючи нгрунтовні знання структури цього ферменту, до теперіш­нього часу немає даних стосовно механізму відкриття «флепів». Саме тому здійснено симуляцію молекулярної динаміки ВІЛ-1 протеази у вакуумі та водному розчині в піко- та наносекундному часових проміжках. Спостерігалося фомування структурного «динамічного» сайта зв'язування як у нс-так і в пс-часових проміжках. «Динамічний» карман утво­рюється, в основному, з гідрофобних амінокислотних залишків, а саме: Val32, Lys45, Ile47, Gly48, Gly49fб Ile50, Gly51, Gly52, Ile54, Val56, Leu76, Gly78, Pro79, Thr80, Pro81. Він залишається добре визначеним впродовж усього періоду симуляїі Пропонується використання цього карману для дизайну лікарських засобів

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