#18 · Structural bio & protein design
MD simulations map residue-level determinants of amyloid aggregation and inhibition
The dominant thread is simulation-based localization of aggregation-determining interfaces at residue resolution. The spermine preprint applies all-atom MD to Tau K18, α-synuclein and Aβ40 and finds residue-specific rather than net-charge-driven control of fibril-like contacts. The KLVFF study simulates an Aβ hexamer, where fibril-end binding destabilizes terminal monomers, and CD and ThT assays support inhibition. The myocilin study combines 21 μs of MD with GaMD to map five aggregation-prone regions in the olfactomedin domain linked to blade A destabilization. What is new is explicit assignment of determinants to specific residues and regions, with modulator and inhibitor effects evaluated against structural contacts. The myocilin case extends this logic beyond canonical amyloid proteins.
Published papers
Molecular Mechanism of Beta-Amyloid Aggregation Inhibition by KLVFF.
MD simulations of an Aβ hexamer with KLVFF show fibril-end binding that destabilizes terminal monomers; CD and ThT assays support inhibition.
Unraveling the Structural Basis for Antibody Synergy against Escape-Resistant Nipah Virus Mutant.
Effective countermeasures are urgently needed to mitigate the potential pandemic threat posed by the highly pathogenic Nipah virus, which is capable of person-t
Enhanced and Classical MD Simulations Map Aggregation-Prone Regions in the Olfactomedin Domain of Myocilin.
21 μs of MD and GaMD simulations map five aggregation-prone regions in myocilin's olfactomedin domain tied to blade A destabilization.
Preprints
Residue-Specific Modulation of Aggregation-Associated Interactions bySpermine in Tau, α-Synuclein, and Aβ40
All-atom MD of spermine on Tau K18, α-synuclein and Aβ40 shows residue-specific, not net-charge-driven, control of fibril-like contacts.
Topic history
| Date | Rank |
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| #18 | |
| #31 | |
| #26 | |
| #31 | |
| #31 | |
| #30 |