Secondary structure dependence of amyloid‐β(1–40) on simulation techniques and force field parameters

Abstract

Our recent studies revealed that none of the selected widely used force field parameters and molecular dynamics simulation techniques yield structural properties for the intrinsically disordered α‐synuclein that are in agreement with various experiments via testing different force field parameters. Here, we extend our studies on the secondary structure properties of the disordered amyloid‐β(1–40) peptide in aqueous solution. For these purposes, we conducted extensive replica exchange molecular dynamics simulations and obtained extensive molecular dynamics simulation trajectories from David E. Shaw group. Specifically, these molecular dynamics simulations were conducted using various force field parameters and obtained results are compared to our replica exchange molecular dynamics simulations and experiments. In this study, we calculated the secondary structure abundances and radius of gyration values for amyloid‐β(1–40) that were simulated using varying force field parameter sets and different simulation techniques. In addition, the intrinsic disorder propensity, as well as sequence‐based secondary structure predisposition of amyloid‐β(1–40) and compared the findings with the results obtained from molecular simulations using various force field parameters and different simulation techniques. Our studies clearly show that the epitope region identification of amyloid‐β(1–40) depends on the chosen simulation technique and chosen force field parameters. Based on comparison with experiments, we find that best computational results in agreement with experiments are obtained using the a99sb*‐ildn, charmm36m, and a99sb‐disp parameters for the amyloid‐β(1–40) peptide in molecular dynamics simulations without parallel tempering or via replica exchange molecular dynamics simulations.

Structures of the Wild-Type and S59L Mutant CHCHD10 Proteins Important in Amyotrophic Lateral Sclerosis–Frontotemporal Dementia

“…We conducted multirun MD simulations of the wild-type and S59L mutant CHCHD10 proteins in water at 310 K temperature using the GROMACS 5.1.4 software package. , The time step was set to 2 fs, the CHARMM36m parameters were used for the IDPRs, and the TIP3P model for was chosen for water. , These parameters yielded results in accordance with the experiments for a model IDP in a previous study. , Iterative threading assembly refinement (I-TASSER) is a hierarchial approach for protein structure prediction and structure-based templates from the PDB by the multiple threading approach LOMETS, with full-length atomic models constructed by iterative template-fragment assembly simulations. Function insights are then derived by rethreading the 3D models through the protein function database BioLIP.…”

“…20,21 These parameters yielded results in accordance with the experiments for a model IDP in a previous study. 22,23 Iterative threading assembly refinement (I-TASSER) is a hierarchial approach for protein structure prediction and structure-based templates from the PDB by the multiple threading approach LOMETS, with full-length atomic models constructed by iterative template-fragment assembly simulations. Function insights are then derived by rethreading the 3D models through the protein function database BioLIP.…”

Effects of the Jokela type of spinal muscular atrophy‐related G66V mutation on the structural ensemble characteristics of CHCHD10

“…The Gromacs 5.1.4 software package was utilized, 12 and the temperature was set to 310K with a time‐step of 2 fs. The TIP3P parameters 13 and CHARMM36m 14 force field parameters were chosen for water and the proteins because these parameters yield findings in accordance with experiments for IDPs 15 . Each protein was solvated by 10 948 water molecules and periodic boundary conditions were applied 16 .…”

“…The TIP3P parameters 13 and CHARMM36m 14 force field parameters were chosen for water and the proteins because these parameters yield findings in accordance with experiments for IDPs. 15 Each protein was solvated by 10 948 water molecules and periodic boundary conditions were applied. 16 For defining the long-range interactions, the Particle Mesh Ewald method was utilized.…”

Frontotemporal Dementia-Related V57E Mutation Impairs Mitochondrial Function and Alters the Structural Properties of CHCHD10

“…We set the temperature to body temperature (310 K) using the Gromacs 5.1.4 software package with a time step of 2 fs . The force field parameters (CHARMM36m for proteins and TIP3P for water) that we presented to yield results for intrinsically disordered proteins in agreement with experiments were selected for the proteins . CHCHD10 WT and CHCHD10 V57E were solvated by 10 948 water molecules.…”