Constructing conformational library for amyloid-β42 dimers as the smallest toxic oligomers using two CHARMM force fields

Interactions of curcumin’s degradation products with the Aβ42 dimer: A computational study

“…The library of A β 42 dimers was generated using the blockwise excursion sampling (BES) protocol, which was recently employed for the construction of a diverse conformational library for A β 42 monomers and dimers (52,53). The BES protocol comprises simulating annealing and many short conventional MD simulations which are called blocks and denoted as Γ SA and Γ MD , respectively.…”

“…We used 1000 excursion chains (N EC = 1000), and built the initial structures of as extended and parallel A β 42 dimers. For more details on this sampling methodology and its terminology see reference (52,53). The A β 42 dimer structures sampled by the BES protocol were clustered using the Daura algorithm (54) with a Carbon alpha (C α ) root-mean-square deviation (RMSD) cutoff of 0.3 nm.…”

“…Then collision cross sections (CCS) values were calculated for all structures. A total of 1183 representative structures of all MD snapshots that satisfied the experimental value of CCS (1252 ± 20 Å 2 ) were selected (52,55) and used as a library of A β 42 dimers for the docking protocol after energy minimization by 5000 iterations of the steepest descent algorithm. The MD simulations were carried out using the GROMACS 5.1.5 software (56- 57).…”

“…In a recent work, we built a diverse conformational library of the A β 42 dimers using the blockwise excursion sampling (BES) and standard CHARMM force fields (52,53). We demonstrated that the conformational library of A β 42 dimers generated by the CHARMM36m force field is in good agreement with experimental data (52). In the present study, we use the generated CHARMM36m library to identify the binding sites of the curcumin degradation products in A β 42 dimers through a new computational pipeline in the framework of the ensemble docking strategy.…”

“…Here, we investigate the effects of the curcumin degradation products (ferulic aldehyde and vanillin) on A β 42 dimers by means of computer simulations. In a recent work, we built a diverse conformational library of the A β 42 dimers using the blockwise excursion sampling (BES) and standard CHARMM force fields (52,53). We demonstrated that the conformational library of A β 42 dimers generated by the CHARMM36m force field is in good agreement with experimental data (52).…”