@article {Sanjeev:2019:1871-5249:24,
title = "Computational Study on the Role of -Synuclein in Inhibiting the -Synuclein Aggregation",
journal = "Central Nervous System Agents in Medicinal ChemistryChemistry - Central Nervous System Agents)",
parent_itemid = "infobike://ben/cnsamc",
publishercode ="ben",
year = "2019",
volume = "19",
number = "1",
publication date ="2019-04-01T00:00:00",
pages = "24-30",
itemtype = "ARTICLE",
issn = "1871-5249",
url = "https://www.ingentaconnect.com/content/ben/cnsamc/2019/00000019/00000001/art00007",
doi = "doi:10.2174/1871524918666181012160439",
keyword = "parkinson's disease, homo-dimer, potential of mean force, self-assembly, Lewy bodies, molecular dynamics",
author = "Sanjeev, Airy and Mattaparthi, Venkata S.K.",
abstract = "Background: -Synuclein (S) is the precursor protein present in Lewy Bodies that helps in the formation of highly ordered amyloid fibrils that is associated with the occurrence of Parkinsons disease, a neuro-degenerative disorder. Many reports have now been focused
on finding the probable targets to weaken this debilitating disease. Recently -synuclein (S), a presynaptic protein, was highlighted to inhibit the aggregation propensity of S both in vivo and in vitro. However the nature, location and specificity of molecular interactions
existing between the S and S is not known in spite of the potential importance of S as an inhibitor of S. Objective: To understand the inhibition of S aggregation by S at the molecular level. Methods: Umbrella sampling method was used along
with molecular dynamics simulation to investigate the conformational dynamics, degree of association and molecular interaction between the monomeric units in the S/S hetero-dimer. Results and Discussion: The dissociation energy barrier for S/S hetero-dimer
was found to be higher than S/S homo-dimer. S can therefore readily form a hetero-dimer by combining with S than forming a homo-dimer. We also observed strong transient interactions involving hydrogen bonds, salt-bridges and non-bonded contacts between the monomeric
units in S/S hetero-dimer. Conclusion: Our findings suggest that S may inhibit the aggregation propensity of S.",
}