Dimerization of Full‐length Aβ ‐42 Peptide: A Comparison of Different Force Fields and WaterModels

Abstract Among the two isoforms of amyloid‐ β i. e., A β ‐40 and A β ‐42, A β ‐42 is more toxic due to its increased aggregation propensity. The oligomerization pathways of amyloid‐ β may be investigated by studying its dimerization process at an atomic level. Intrinsically disordered proteins (IDPs) lack well‐defined structures and are associated with numerous neurodegenerative disorders. Molecular dynamics simulations of these proteins are often limited by the choice of parameters due to inconsistencies in the empirically developed protein force fields and water models. To evaluate the accuracy of recently developed force fields for IDPs, we study the dimerization of full‐length A β ‐42 in aqueous solution with three different combinations of AMBER force field parameters and water models such as ff14SB/TIP3P, ff19SB/OPC, and ff19SB/TIP3P using classical MD and Umbrella Sampling method. This work may be used as a benchmark to compare the performance of different force fields for the simulations of IDPs.