Number of the records: 1
Computational investigation on the effect of the peptidomimetic inhibitors (NPT100-18A and NPT200-11) on the α-synuclein and lipid membrane interactions
- 1.
SYSNO ASEP 0578423 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Computational investigation on the effect of the peptidomimetic inhibitors (NPT100-18A and NPT200-11) on the α-synuclein and lipid membrane interactions Author(s) Das, D. (IN)
Bharadwaz, Priyam (UFCH-W) SAI
Mattaparthi, V. S. K. (IN)Source Title Journal of Biomolecular Structure & Dynamics. - : Taylor & Francis - ISSN 0739-1102
(2023)Number of pages 10 s. Language eng - English Country GB - United Kingdom Keywords molecular-dynamics simulations ; lewy body disease ; parkinsons-disease ; force-field ; basis-sets ; system ; oligomerization ; accumulation ; mutations ; mechanism ; alpha-Synuclein aggregation ; membrane dynamics ; dft ; npt100-18a ; npt200-11 OECD category Physical chemistry Method of publishing Limited access Institutional support UFCH-W - RVO:61388955 UT WOS 001077480000001 EID SCOPUS 85173948923 DOI 10.1080/07391102.2023.2262599 Annotation Parkinson's disease (PD) is associated with alpha-synuclein (alpha-Syn), a presynaptic protein that binds to cell membranes. The molecular pathophysiology of PD most likely begins with the binding of alpha-Syn to membranes. Recently, two peptidomimetic inhibitors (NPT100-18A and NPT200-11) were identified to potentially interact with alpha-Syn and affect the interaction of alpha-Syn with the membrane. In this study, the effect of the two peptidomimetic inhibitors on the alpha-Syn-membrane interaction was demonstrated. DFT calculations were performed for optimization of the two inhibitors, and the nucleophilicity (N) and electrophilicity (omega) of NPT100-18A and NPT200-11 were calculated to be 3.90 and 3.86 (N), 1.06 and 1.04 (omega), respectively. Using the docking tool (CB-dock2), the two alpha-Syn-peptidomimetic inhibitor complexes (alpha-Syn-NPT100-18A and alpha-Syn-NPT200-11) have been prepared. Then all-atom molecular dynamics (MD) simulation was carried out on the alpha-Syn (control), alpha-Syn-NPT100-18A and alpha-Syn-NPT200-11 complex systems in presence of DOPE: DOPS: DOPC (5:3:2) lipid bilayer. From the conformational dynamics analysis, the 3-D structure of alpha-Syn was found to be stable, and the helices present in the regions (1-37) and (45-95) of alpha-Syn were found to be retained in the presence of the two peptidomimetic inhibitors. The electron density profile analysis revealed the binding modes of NAC and C-terminal region of alpha-Syn (in the presence of NPT200-11 inhibitor) with lipid membrane are in the close vicinity from the lipid bilayer centre. Our findings in this study on alpha-Syn-membrane interactions may be useful for developing a new therapeutic approach for treating PD and other neurodegenerative disorders. Workplace J. Heyrovsky Institute of Physical Chemistry Contact Michaela Knapová, michaela.knapova@jh-inst.cas.cz, Tel.: 266 053 196 Year of Publishing 2025 Electronic address https://www.tandfonline.com/doi/abs/10.1080/07391102.2023.2262599
Number of the records: 1