02343nas a2200253   4500008004100000022001400041245009300055210006900148260000800217300001400225490000700239520147400246653003501720653002401755653002501779653002801804653003001832653002301862100002501885700002301910700001801933700001501951856012301966       2022                        eng d  a1948-719300aScan-find-scan-model: discrete site-targeted suppressor design strategy for amyloid-beta0 aScanfindscanmodel discrete sitetargeted suppressor design strate  cJUL  a2191-22080 v133 a<p>
	Alzheimer's disease is undoubtedly the most well-studied ranks at the top in terms of getting attention from the scientific community for structural property-based characterization. Even after decades of extensive research, there is existing volatility in terms of understanding and hence the effective tackling procedures against the disease that arises due to the lack of knowledge of both specific targetand site-specific drugs. Here, we develop a multidimensional approach based on the characterization of the common static-dynamic-thermodynamic trait of the monomeric protein, which efficiently identifies a small target sequence that contains an inherent tendency to misfold and consequently aggregate. The robustness of the identification of the target sequence comes with an abundance of a priori knowledge about the length and sequence of the target and hence guides toward effective designing of the target-specific drug with a very low probability of bottleneck and failure. Based on the target sequence information, we further identified a specific mutant that showed the maximum potential to act as a destabilizer of the monomeric protein as well as enormous success as an aggregation suppressor. We eventually tested the drug efficacy by estimating the extent of modulation of binding affinity existing within the fibrillar form of the A beta protein due to a single-point mutation and hence provided a proof of concept of the entire protocol.</p>
10aconfigurational misfoldability10adrug developability10ainherent frustration10apotential aggregability10asequence-based mutability10atarget specificity1 aBhagavatula, Hasathi1 aSarkar, Archishman1 aSantra, Binit1 aDas, Atanu  uhttps://library.ncl.res.in/content/scan-find-scan-model-discrete-site-targeted-suppressor-design-strategy-amyloid-beta