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Inhibition mechanisms of a pyridazine-based amyloid inhibitor: as a β-sheet destabilizer and a helix bridge maker
, Article Journal of Physical Chemistry B ; Volume 121, Issue 32 , 2017 , Pages 7633-7645 ; 15206106 (ISSN) ; Jabbari, M. P ; Sharif University of Technology
Abstract
Conformational diseases have been investigated extensively in recent years; as a result, a number of drug candidates have been introduced as amyloid inhibitors; however, no effective therapies have been put forward. RS-0406 with pyridazine as its core chemical structure has so far shown promising results in inhibiting amyloid formation. In the present work, using molecular dynamics, we undertook the investigation of RS-0406 interactions with U-shaped Aβ1−42 and Aβ1−40 pentamers, Aβ1−42 monomers, and double-horseshoe-like Aβ1−42. To set better parameters for the small molecule, experimental and computational log P values were obtained. In addition, an analogue of RS-0406 was also simulated...
Investigating reliable conditions for hewl as an amyloid model in computational studies and drug interactions
, Article Journal of Chemical Information and Modeling ; Volume 59, Issue 12 , 2019 , Pages 5218-5229 ; 15499596 (ISSN) ; Jabbary, M ; Sharif University of Technology
American Chemical Society
2019
Abstract
A number of conformational diseases in humans have been associated with protein/peptide fibrillation known as amyloid. Although extensive studies have been conducted in understanding the molecular basis of amyloid formation, a detailed mechanism is still missing. Experimentally, HEWL (hen egg white lysozyme) has been exploited ubiquitously as a model protein for amyloid fibrillation and drug inhibition. However, computational studies investigating fibril formation of HEWL have been a difficult task to perform mainly due to high stability of lysozymes and the absence of crystal structures of HEWL fibril oligomers. In this study, we have examined various conditions of HEWL amyloid formation...