Molecular dynamics simulations of water and biomolecules with a Monte Carlo constant pressure algorithm

Åqvist, Johan; Wennerström, Petra; Nervall, Martin; Bjelic, Sinisa; Brandsdal, Bjørn Olav

doi:10.1016/j.cplett.2003.12.039

Cited by 360 publications

(315 citation statements)

References 25 publications

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“…The target temperature was set to 303.15K by the use of the Langevin thermostat (Goga et al , ) with a collision frequency of 1 ps −1 . The desired pressure of 1.0 bar was maintained by the Monte Carlo barostat (Åqvist et al , ). Non‐bonded interactions were described up until a distance of 8 Å, and the particle mesh Ewald method (Darden et al , ) was used to describe long‐range effects.…”

Section: Methodsmentioning

confidence: 99%

Extracellular interface between APP and Nicastrin regulates Aβ length and response to γ‐secretase modulators

et al. 2019

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γ‐Secretase complexes ( GSEC s) are multimeric membrane proteases involved in a variety of physiological processes and linked to Alzheimer's disease ( AD ). Presenilin ( PSEN , catalytic subunit), Nicastrin ( NCT ), Presenilin Enhancer 2 ( PEN ‐2), and Anterior Pharynx Defective 1 ( APH 1) are the essential subunits of GSEC s. Mutations in PSEN and the Amyloid Precursor Protein ( APP ) cause early‐onset AD . GSEC s successively cut APP to generate amyloid‐β (Aβ) peptides of various lengths. AD ‐causing mutations destabilize GSEC ‐ APP /Aβ n interactions and thus enhance the production of longer Aβs, which elicit neurotoxic events underlying pathogenesis. Here, we investigated the molecular strategies that anchor GSEC and APP /Aβ n during the sequential proteolysis. Our studies reveal that a direct interaction between NCT ectodomain and APP C99 influences the stability of GSEC ‐Aβn assemblies and thereby modulates Aβ length. The data suggest a potential link between single‐nucleotide variants in NCSTN and AD risk. Furthermore, our work indicates that an extracellular interface between the protease ( NCT , PSEN ) and the substrate ( APP ) represents the target for compounds ( GSM s) modulating Aβ length. Our findings may guide future rationale‐based drug discovery efforts.

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Section: Methodsmentioning

confidence: 99%

Extracellular interface between APP and Nicastrin regulates Aβ length and response to γ‐secretase modulators

et al. 2019

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“…For both sets (MD‐LB and MD‐RB), the restraint free MD simulations were carried out using OpenMM under the same simulation conditions used in the 2D‐WEUSMD simulation. The temperature and the pressure were controlled by Langevin dynamics with a friction coefficient 1 ps −1 and a semi‐isotropic Monte Carlo barostat with a pressure coupling frequency of 100 steps. We used the OpenMM input scripts generated by CHARMM‐GUI Membrane Builder …”

Section: Methodsmentioning

confidence: 99%

U‐shaped caveolin‐1 conformations are tightly regulated by hydrogen bonds with lipids

Park

Glover

2019

J Comput Chem

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The structure and dynamics of a truncated (residues 82–136) caveolin‐1 (Cav1) construct having a helix‐break‐helix motif are explored by both all‐atom free energy and molecular dynamics (MD) simulations in an explicit bilayer membrane. Two stable Cav1 conformations with small (LB‐Cav1) and large hinge angles (RB‐Cav1) between two helices are identified although their relative free energy cannot be reliably estimated due to the sampling issues. RB‐Cav1s contain one or two lipids residing between the helices that are hydrogen bonded (h‐bonded) to both helices in a multidentate fashion. LB‐Cav1s show the helices with mono‐dentate lipid h‐bond interactions or multidentate interactions limited to a single helix at most. The two conformational states of Cav1 remain their initial state during 2‐μs MD simulation, suggesting that there is a significant hidden barrier (other than the insertion depth of Cav1 and its hinge angle) and the Cav1 conformational states are tightly regulated by the h‐bonds between Cav1 and lipids along with the associated lipid rearrangement during the course of Cav1 conformational changes. © 2019 Wiley Periodicals, Inc.

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“…19–20 It does this by periodically rescaling the box, computing the change in energy, then accepting or rejecting the change based on a Metropolis criterion.…”

Section: Standard Features and Platformsmentioning

confidence: 99%

OpenMM 4: A Reusable, Extensible, Hardware Independent Library for High Performance Molecular Simulation

Eastman

Friedrichs

Chodera

et al. 2012

J. Chem. Theory Comput.

647

662

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OpenMM is a software toolkit for performing molecular simulations on a range of high performance computing architectures. It is based on a layered architecture: the lower layers function as a reusable library that can be invoked by any application, while the upper layers form a complete environment for running molecular simulations. The library API hides all hardware-specific dependencies and optimizations from the users and developers of simulation programs: they can be run without modification on any hardware on which the API has been implemented. The current implementations of OpenMM include support for graphics processing units using the OpenCL and CUDA frameworks. In addition, OpenMM was designed to be extensible, so new hardware architectures can be accommodated and new functionality (e.g., energy terms and integrators) can be easily added.

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Molecular dynamics simulations of water and biomolecules with a Monte Carlo constant pressure algorithm

Cited by 360 publications

References 25 publications

Extracellular interface between APP and Nicastrin regulates Aβ length and response to γ‐secretase modulators

Extracellular interface between APP and Nicastrin regulates Aβ length and response to γ‐secretase modulators

U‐shaped caveolin‐1 conformations are tightly regulated by hydrogen bonds with lipids

OpenMM 4: A Reusable, Extensible, Hardware Independent Library for High Performance Molecular Simulation

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