A Core Outcome Set for Nonpharmacological Community-Based Interventions for People Living With Dementia at Home: A Systematic Review of Outcome Measurement Instruments

Andrew J.E. Harding, Hazel Morbey, Faraz Ahmed, Carol Opdebeeck, Ruth Elvish, Iracema Leroi, Paula R. Williamson, John Keady, Siobhan Reilly

Research output: Contribution to journalArticlepeer-review

Abstract

Predicting the binding mode of flexible polypeptides to proteins is an important task that falls outside the domain of applicability of most small molecule and protein−protein docking tools. Here, we test the small molecule flexible ligand docking program Glide on a set of 19 non-α-helical peptides and systematically improve pose prediction accuracy by enhancing Glide sampling for flexible polypeptides. In addition, scoring of the poses was improved by post-processing with physics-based implicit solvent MM- GBSA calculations. Using the best RMSD among the top 10 scoring poses as a metric, the success rate (RMSD ≤ 2.0 Å for the interface backbone atoms) increased from 21% with default Glide SP settings to 58% with the enhanced peptide sampling and scoring protocol in the case of redocking to the native protein structure. This approaches the accuracy of the recently developed Rosetta FlexPepDock method (63% success for these 19 peptides) while being over 100 times faster. Cross-docking was performed for a subset of cases where an unbound receptor structure was available, and in that case, 40% of peptides were docked successfully. We analyze the results and find that the optimized polypeptide protocol is most accurate for extended peptides of limited size and number of formal charges, defining a domain of applicability for this approach.
Original languageEnglish
JournalThe Gerontologist
Early online date25 Jun 2020
DOIs
Publication statusPublished - 25 Jun 2020

Keywords

  • Dementia
  • Alzheimer's disease
  • measurement
  • Outcome
  • core outcome set

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