Conformational dynamics of functionally important loops of HIV-1 gp120 probed by molecular dynamics simulations
Mokkila, Sini (2015)
2015
Teknis-luonnontieteellinen koulutusohjelma
Luonnontieteiden tiedekunta - Faculty of Natural Sciences
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Hyväksymispäivämäärä
2015-05-06
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:tty-201504271246
https://urn.fi/URN:NBN:fi:tty-201504271246
Tiivistelmä
Acquired immunodeficiency syndrome (AIDS) is a life-threatening disease caused by human immunodeficiency viruses (HIVs). A protective vaccination has been under development for several decades. The main targets for the vaccines are surface glycoproteins (gp120) on the viral envelope of HIV-1. Gp120 is characterized by functionally important variable (V) loops that are hard to study experimentally.
Here, atomistic molecular dynamics (MD) simulations are harnessed to improve the current understanding of the gp120 loop dynamics. According to previous MD studies the major variable loop V3 shows significant flexibility in monomeric gp120. This is also observed in this study. Additionally, the flexibility of the V1/V2 domain in monomeric gp120 is demonstrated for the first time. However, gp120 in the trimer context tells a different story. According to the simulations, the major variable loops have lost their flexibility, mobility, and concerted motion among the loops in the trimer. The reduced motion seems to be due to inter-gp120 interactions, where the V2 and V3 loops play key roles in stabilizing the trimer apex.
The results provide significant insight into gp120 variable loop dynamics on an atomic level in the native trimeric state and facilitate understanding the mechanism of the viral entry and its inhibition.
Here, atomistic molecular dynamics (MD) simulations are harnessed to improve the current understanding of the gp120 loop dynamics. According to previous MD studies the major variable loop V3 shows significant flexibility in monomeric gp120. This is also observed in this study. Additionally, the flexibility of the V1/V2 domain in monomeric gp120 is demonstrated for the first time. However, gp120 in the trimer context tells a different story. According to the simulations, the major variable loops have lost their flexibility, mobility, and concerted motion among the loops in the trimer. The reduced motion seems to be due to inter-gp120 interactions, where the V2 and V3 loops play key roles in stabilizing the trimer apex.
The results provide significant insight into gp120 variable loop dynamics on an atomic level in the native trimeric state and facilitate understanding the mechanism of the viral entry and its inhibition.