Constant pressure molecular dynamics simulation: The Langevin piston method

Feller, Scott E.; Zhang, Yuhong; Pastor, Richard W.; Brooks, Bernard R.

doi:10.1063/1.470648

Cited by 4,007 publications

(3,487 citation statements)

References 13 publications

Supporting

Mentioning

3,401

Contrasting

Unclassified

Order By: Relevance

“…Possibly, this difference translates into the different inhibition behavior of the two isomers with respect to β-amyloid-aggregation. The similar IC 50 values, on the other hand, might be due to enthalpy−entropy compensation: While the ring-opened form shows good enthalpic interactions (also with water molecules) at the cost of an entropy loss, the residual flexibility of the ring-closed form reduces the entropy loss, but gains less enthalpy. Obviously, this is only a qualitative interpretation of the observations made in the simulation studies.…”

Section: ■ Results and Discussionmentioning

confidence: 99%

Acetylcholinesterase Inhibitors with Photoswitchable Inhibition of β-Amyloid Aggregation

Chen

Wehle

Kuzmanovic³

et al. 2014

ACS Chem. Neurosci.

102

103

View full text Add to dashboard Cite

Photochromic cholinesterase inhibitors were obtained from cis-1,2-α-dithienylethene-based compounds by incorporating one or two aminopolymethylene tacrine groups. All target compounds are potent acetyl-(AChE) and butyrylcholinesterase (BChE) inhibitors in the nanomolar concentration range. Compound 11b bearing an octylene linker exhibited interactions with both the catalytic active site (CAS) and the peripheral anionic site (PAS) of AChE. Yet upon irradiation with light, the mechanism of interaction varied from one photochromic form to another, which was investigated by kinetic studies and proved "photoswitchable". The AChE-induced β-amyloid (Aβ) aggregation assay gave further experimental support to this finding: Aβ 1−40 aggregation catalyzed by the PAS of AChE might be inhibited by compound 11b in a concentration-dependent manner and seems to occur only with one photochromic form. Computational docking studies provided potential binding modes of the compound. Docking studies and molecular dynamics (MD) simulations for the ringopen and -closed form indicate a difference in binding. Although both forms can interact with the PAS, more stable interactions are observed for the ring-open form based upon stabilization of a water molecule network within the enzyme, whereas the ringclosed form lacks the required conformational flexibility for an analogous binding mode. The photoswitchable inhibitor identified might serve as valuable molecular tool to investigate the different biological properties of AChE as well as its role in pathogenesis of AD in in vitro assays.

show abstract

Section: ■ Results and Discussionmentioning

confidence: 99%

Acetylcholinesterase Inhibitors with Photoswitchable Inhibition of β-Amyloid Aggregation

Chen

Wehle

Kuzmanovic³

et al. 2014

ACS Chem. Neurosci.

102

103

View full text Add to dashboard Cite

show abstract

“…The temperature was fixed at 277 or 313 K, for the low and high temperature simulations, respectively, using Langevin dynamics, 63 whereas pressure was held constant at 1 ATM through the Langevin piston method. 64 The SHAKE 65 and SETTLE 66 algorithms were used to restrain bond lengths, for nucleic acid and water molecules, respectively. The atomic positions were saved every 250 steps (i.e., 0.5 ps) for the analyses.…”

Section: Methodsmentioning

confidence: 99%

Temperature-Controlled Encapsulation and Release of an Active Enzyme in the Cavity of a Self-Assembled DNA Nanocage

et al. 2013

View full text Add to dashboard Cite

We demonstrate temperature-controlled encapsulation and release of the enzyme horseradish peroxidase using a preassembled and covalently closed three-dimensional DNA cage structure as a controllable encapsulation device. The utilized cage structure was covalently closed and composed of 12 double-stranded B-DNA helices that constituted the edges of the structure. The double stranded helices were interrupted by short single-stranded thymidine linkers constituting the cage corners except for one, which was composed by four 32 nucleotide long stretches of DNA with a sequence that allowed them to fold into hairpin structures. As demonstrated by gel-electrophoretic and fluorophore-quenching experiments this design imposed a temperature-controlled conformational transition capability to the structure, which allowed entrance or release of an enzyme cargo at 37 °C while ensuring retainment of the cargo in the central cavity of the cage at 4 °C. The entrapped enzyme was catalytically active inside the DNA cage and was able to convert substrate molecules penetrating the apertures in the DNA lattice that surrounded the central cavity of the cage.

show abstract

“…Pressure was maintained at 1 atm using the Langevin piston method. 60 From this point on, the volume was kept constant and the system was tested for 20 ps of classical MD. To avoid hypothetical biases taking place in the equilibration stage, each production run was independently equilibrated.…”

Section: Simulation Detailsmentioning

confidence: 99%

Potentially amyloidogenic conformational intermediates populate the unfolding landscape of transthyretin: Insights from molecular dynamics simulations

et al. 2010

View full text Add to dashboard Cite

Protein aggregation into insoluble fibrillar structures known as amyloid characterizes several neurodegenerative diseases, including Alzheimer's, Huntington's and Creutzfeldt-Jakob. Transthyretin (TTR), a homotetrameric plasma protein, is known to be the causative agent of amyloid pathologies such as FAP (familial amyloid polyneuropathy), FAC (familial amyloid cardiomiopathy) and SSA (senile systemic amyloidosis). It is generally accepted that TTR tetramer dissociation and monomer partial unfolding precedes amyloid fibril formation. To explore the TTR unfolding landscape and to identify potential intermediate conformations with high tendency for amyloid formation, we have performed molecular dynamics unfolding simulations of WT-TTR and L55P-TTR, a highly amyloidogenic TTR variant. Our simulations in explicit water allow the identification of events that clearly discriminate the unfolding behavior of WT and L55P-TTR. Analysis of the simulation trajectories show that (i) the L55P monomers unfold earlier and to a larger extent than the WT; (ii) the single a-helix in the TTR monomer completely unfolds in most of the L55P simulations while remain folded in WT simulations; (iii) L55P forms, early in the simulations, aggregation-prone conformations characterized by full displacement of strands C and D from the main b-sandwich core of the monomer; (iv) L55P shows, late in the simulations, severe loss of the H-bond network and consequent destabilization of the CBEF b-sheet of the b-sandwich; (v) WT forms aggregationcompatible conformations only late in the simulations and upon extensive unfolding of the monomer. These results clearly show that, in comparison with WT, L55P-TTR does present a much higher probability of forming transient conformations compatible with aggregation and amyloid formation.

show abstract

Constant pressure molecular dynamics simulation: The Langevin piston method

Cited by 4,007 publications

References 13 publications

Acetylcholinesterase Inhibitors with Photoswitchable Inhibition of β-Amyloid Aggregation

Acetylcholinesterase Inhibitors with Photoswitchable Inhibition of β-Amyloid Aggregation

Temperature-Controlled Encapsulation and Release of an Active Enzyme in the Cavity of a Self-Assembled DNA Nanocage

Potentially amyloidogenic conformational intermediates populate the unfolding landscape of transthyretin: Insights from molecular dynamics simulations

Contact Info

Product

Resources

About