GLY 230 / Glycadia - LARVOL DELTA

Unravelling the molecular basis of AM-6494 high potency at BACE1 in Alzheimer's disease: an integrated dynamic interaction investigation. (PubMed, J Biomol Struct Dyn) - "To elucidate the binding mechanism of AM-6494 relative to umibecestat (CNP-520) as well as the structural changes when bound to BACE1, advanced computational techniques such as accelerated MD simulation and principal component analysis have been utilised. Besides the catalytic Asp32/228 dyad, Tyr14, Leu30, Tyr71 and Gly230 represent critical residues in the potency of these inhibitors at BACE1 binding interface. The findings highlighted in this research provide a basis to explain AM-6494 high inhibitory potency and might assist in the design of new inhibitors with improved selectivity and potency for BACE1."

Journal • Alzheimer's Disease • CNS Disorders

Binding Mechanism of Thrombin-Ligand Systems Investigated by Polarized Protein-Specific Charge Force Field and Interaction Entropy Method. (PubMed, J Phys Chem B) - "Furthermore, the binding free energy and hot-spot residue energy are decomposed, and the common hot-spot residues in the two groups of systems are Trp50, Leu96, Ile179, Asp199, Cyx201, Ser226, Trp227, Gly228, and Gly230. This study demonstrates that the new IE method is superior to the Nmode method in predicting binding free energy and emphasizes the importance of electronic polarization in molecular dynamics simulation. Moreover, from the viewpoint of energy and structure analysis, this study reveals the origin of the change in binding free energy in modified ligands with different binding sites."

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