A partial nudged elastic band implementation for use with large or explicitly solvated systems

Bergonzo, Christina; Campbell, Arthur J.; Walker, Ross C.; Simmerling, Carlos

doi:10.1002/qua.22405

Cited by 46 publications

(71 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The nudged elastic band method using simulated annealing was used to map a pathway from I 2 to the hybrid form using multisander as per the AMBER website [85], 192 images were used and tgtfitmask=“:1–24” including the tetrad core potassium ions and tgtrmsmask=“:1–22@P,O1P,O2P,O5',O3'” were used. The endpoints were set as the chair and corresponding hybrid form.…”

Section: Methodsmentioning

confidence: 99%

Folding and Unfolding Pathways of the Human Telomeric G-Quadruplex

Gray

Trent

Chaires

2014

Journal of Molecular Biology

167

238

View full text Add to dashboard Cite

Sequence analogues of human telomeric DNA such as d[AGGG(TTAGGG)3] (Tel22) fold into monomeric quadruplex structures in the presence of a suitable cation. To investigate the pathway for unimolecular quadruplex formation, we monitored the kinetics of K+-induced folding of Tel22 by circular dichroism (CD), intrinsic 2-aminopurine fluorescence, and fluorescence resonance energy transfer (FRET). The results are consistent with a four-step pathway U ↔ I1 ↔ I2 ↔ I3 ↔ F where U and F represent unfolded and folded conformational ensembles, and I1, I2, and I3 are intermediates. Previous kinetic studies have shown that I1 is formed in a rapid pre-equilibrium and may consist of an ensemble of “prefolded” hairpin structures brought about by cation-induced electrostatic collapse of the DNA. The current study shows that I1 converts to I2 with a relaxation time τ1 = 0.1 s at 25 °C in 25 mM KCl. The CD spectrum of I2 is characteristic of an antiparallel quadruplex that could form as a result of intra-molecular fold-over of the I1 hairpins. I3 is relatively slowly formed (τ2 ≈ 3700 s) and has CD and FRET properties consistent with those expected of a triplex structure as previously observed in equilibrium melting studies. I3 converts to F with τ3 ≈ 750 s. Identical pathways with different kinetic constants involving a rapidly formed antiparallel intermediate were observed with oligonucleotides forming mixed parallel/antiparallel hybrid-1 and hybrid-2 topologies (e.g. d[TTGGG(TTAGGG)3A and d[TAGGG(TTAGGG)3TT]). Aspects of the kinetics of unfolding were also monitored by the spectroscopic methods listed above and by time-resolved fluorescence lifetime measurements using a complementary strand trap assay. These experiments reveal a slow, rate-limiting step along the unfolding pathway.

show abstract

Section: Methodsmentioning

confidence: 99%

Folding and Unfolding Pathways of the Human Telomeric G-Quadruplex

Gray

Trent

Chaires

2014

Journal of Molecular Biology

167

238

View full text Add to dashboard Cite

show abstract

“…The NEB method [27,28] was used to investigate the conformational transition pathway for the transformation between the apo and compound 1-bound MGL. In the NEB method, the transition pathway for a conformational change is connected by a string of replicas (or 'images') of the system.…”

Section: Neb Simulationmentioning

confidence: 99%

Conformational Transition Pathway in the Inhibitor Binding Process of Human Monoacylglycerol Lipase

Chen

Tian

et al. 2014

Protein J

View full text Add to dashboard Cite

Human monoacylglycerol lipase (MGL) catalyzes the hydrolysis of 2-arachidonoylglycerol to arachidonic and glycerol, which plays a pivotal role in the normal biological processes of brain. Co-crystal structure of the MGL in complex with its inhibitor, compound 1, shows that the helix a4 undergoes large-scale conformational changes in response to the compound 1 binding compared to the apo MGL. However, the detailed conformational transition pathway of the helix a4 in the inhibitor binding process of MGL has remained unclear. Here, conventional molecular dynamics (MD) and nudged elastic band (NEB) simulations were performed to explore the conformational transition pathway of the helix a4. Conventional MD simulations unveiled that the compound 1 induced the closed conformation of the active site of MGL, reduced the conformational flexibility of the helix a4, and elicited the large-scale conformational rearrangement of the helix a4, leading to the complete folding of the helix a4. Moreover, NEB simulations revealed that the conformational transition pathway of helix a4 underwent an almost 180°c ounter-clockwise rotation of the helix a4. Our computational results advance the structural and mechanistic understanding of the inhibitory mechanism.

show abstract

“…The partial nudged elastic band method (PNEB)[25], [26] requires an identical number of atoms in each replica of the band. Therefore, the DNA sequence in the final model was changed to match the DNA construct for the initial model.…”

Section: Methodsmentioning

confidence: 99%

Alkylpurine Glycosylase D Employs DNA Sculpting as a Strategy to Extrude and Excise Damaged Bases

Kossmann

Ivanov

2014

PLoS Comput Biol

View full text Add to dashboard Cite

Alkylpurine glycosylase D (AlkD) exhibits a unique base excision strategy. Instead of interacting directly with the lesion, the enzyme engages the non-lesion DNA strand. AlkD induces flipping of the alkylated and opposing base accompanied by DNA stack compression. Since this strategy leaves the alkylated base solvent exposed, the means to achieve enzymatic cleavage had remained unclear. We determined a minimum energy path for flipping out a 3-methyl adenine by AlkD and computed a potential of mean force along this path to delineate the energetics of base extrusion. We show that AlkD acts as a scaffold to stabilize three distinct DNA conformations, including the final extruded state. These states are almost equivalent in free energy and separated by low barriers. Thus, AlkD acts by sculpting the global DNA conformation to achieve lesion expulsion from DNA. N-glycosidic bond scission is then facilitated by a backbone phosphate group proximal to the alkylated base.

show abstract

A partial nudged elastic band implementation for use with large or explicitly solvated systems

Cited by 46 publications

References 27 publications

Folding and Unfolding Pathways of the Human Telomeric G-Quadruplex

Folding and Unfolding Pathways of the Human Telomeric G-Quadruplex

Conformational Transition Pathway in the Inhibitor Binding Process of Human Monoacylglycerol Lipase

Alkylpurine Glycosylase D Employs DNA Sculpting as a Strategy to Extrude and Excise Damaged Bases

Contact Info

Product

Resources

About