Multicanonical molecular dynamics simulations of the N-terminal domain of protein L9

Yaşar, Fatih; Jiang, Ping; Hansmann, Ulrich H. E.

doi:10.1209/0295-5075/105/30008

Cited by 4 publications

(5 citation statements)

References 29 publications

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“…Calculations were performed using an analytical continuum electrostatic (ACE) type model using the Born radius of each atom and a surface tension parameter of 2.26 kJ/mol.nm 2 . [44] The Generalised Born model has been known to overestimate the stability of inter-residue interactions, [45][46][47] but has also been shown to accurately treat solvent effects in simulating proteins [48][49][50] even when such proteins are stabilised by solvent effects. [51,52] Accordingly, we make use of this implicit solvent model in order to reach the requisite time and length scales to observe peptide self-assembly, but -as detailed in Section 3.3 -we employed a rescaled version of the CHARMM27 force field in which the Lennard-Jones and Coulomb interactions were scaled such that intramolecular free energy landscapes for both the peptide monomer and the dimerisation free energy pathway in implicit solvent reproduced those computed under explicit solvation.…”

Section: Implicit Solvent Simulationsmentioning

confidence: 99%

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

Thurston

Tovar

Ferguson

2016

Molecular Simulation

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Synthetic oligopeptides containing π -conjugated cores self-assemble novel materials with attractive electronic and photophysical properties. All-atom, explicit solvent molecular dynamics simulations of Asp-Phe-Ala-Gly-OPV3-Gly-Ala-Phe-Asp peptides were used to parameterise an implicit solvent model to simulate early-stage self-assembly. Under low-pH conditions, peptides assemble into β-sheet-like stacks with strongly favorable monomer association free energies of F ≈ −25k B T . Aggregation at high-pH produces disordered aggregates destabilised by Coulombic repulsion between negatively charged Asp termini ( F ≈ −5k B T ). In simulations of hundreds of monomers over 70 ns we observe the spontaneous formation of up to undecameric aggregates under low-pH conditions. Modeling assembly as a continuoustime Markov process, we infer transition rates between different aggregate sizes and microsecond relaxation times for early-stage assembly. Our data suggests a hierarchical model of assembly in which peptides coalesce into small clusters over tens of nanoseconds followed by structural ripening and diffusion limited aggregation on longer time scales. This work provides new molecular-level understanding of early-stage assembly, and a means to study the impact of peptide sequence and aromatic core chemistry upon the thermodynamics, assembly kinetics, and morphology of the supramolecular aggregates. ARTICLE HISTORY

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Section: Implicit Solvent Simulationsmentioning

confidence: 99%

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

Thurston

Tovar

Ferguson

2016

Molecular Simulation

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“…For instance, simulations suffer from the problem that the assembly of misfolded proteins into oligomers and fibrils happens on time scales (seconds to days) that are beyond the reach of most all-atom molecular dynamics simulations. Hence, exhaustive explorations of protein aggregate landscapes are rarely possible, disallowing often the calculation of the relative weight of the various structures and the pathways connecting them. , In principle, this sampling problem can be alleviated by using replica-exchange-molecular dynamics and other generalized-ensemble techniques, , where the computational costs grow no longer exponentially with protein size but only as a power law. However, the exponent is of order four, and prefactors can be large, effectively restricting the application of these methods to systems much smaller than desired.…”

Section: Introductionmentioning

confidence: 99%

Fibril–Barrel Transitions in Cylindrin Amyloids

Zhang

Hansmann

et al. 2017

J. Chem. Theory Comput.

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We introduce Replica-Exchange-with-Tunneling (RET) simulations as a tool for studies of the conversion between polymorphic amyloids. For the 11-residue amyloid-forming cylindrin peptide we show that this technique allows for a more efficient sampling of the formation and interconversion between fibril-like and barrel-like assemblies. We describe a protocol for optimized analysis of RET simulations that allows us to propose a mechanism for formation and interconversion between various cylindrin assemblies. Especially, we show that an interchain salt bridge between residues K3 and D7 is crucial for formation of the barrel structure.

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“…Until now, there are also lots of work on a particular fragment of the intact protein (residue 1‐39, referred to as NTL9 39 ). Some interesting conclusions are drawn 16,18,73‐78 . This small protein NTL9 39 has been found to be able to fold independently in the solvent 79 .…”

Section: Introductionmentioning

confidence: 92%

Investigating the folding mechanism of the N‐terminal domain of ribosomal protein L9

Zhang

Chen

2021

Proteins

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Protein folding is a popular topic in the life science. However, due to the limited sampling ability of experiments and simulations, the general folding mechanism is not yet clear to us. In this work, we study the folding of the N‐terminal domain of ribosomal protein L9 (NTL9) in detail by a mixing replica exchange molecular dynamics method. The simulation results are close to previous experimental observations. According to the Markov state model, the folding of the protein follows a nucleation‐condensation path. Moreover, after the comparison to its 39‐residue β‐α‐β motif, we find that the helix at the C‐terminal has a great influence on the folding process of the intact protein, including the nucleation of the key residues in the transition state ensemble and the packing of the hydrophobic residues in the native state.

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Multicanonical molecular dynamics simulations of the N-terminal domain of protein L9

Cited by 4 publications

References 29 publications

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

Thermodynamics, morphology, and kinetics of early-stage self-assembly of π-conjugated oligopeptides

Fibril–Barrel Transitions in Cylindrin Amyloids

Investigating the folding mechanism of the N‐terminal domain of ribosomal protein L9

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