A temperature predictor for parallel tempering simulations

Patriksson, Alexandra; Spoel, David van der

doi:10.1039/b716554d

Cited by 461 publications

(497 citation statements)

References 43 publications

Supporting

Mentioning

494

Contrasting

Unclassified

Order By: Relevance

“…The REMD simulation 69 was conducted with 64 replicas with temperature ranging from 315 to 450 K by using the method developed by Patriksson and van der Spoel. 70 Temperatures were controlled by the Bussi−Donadio−Parrinello velocity rescaling thermostat found to sample the canonical ensemble. 71 Exchanges between neighboring replicas were attempted every 2 ps, leading to an average acceptance ratio of 39.4%.…”

Section: ■ Methodsmentioning

confidence: 99%

Atomic and Dynamic Insights into the Beneficial Effect of the 1,4-Naphthoquinon-2-yl-l-tryptophan Inhibitor on Alzheimer’s Aβ1–42 Dimer in Terms of Aggregation and Toxicity

Zhang

et al. 2013

ACS Chem. Neurosci.

View full text Add to dashboard Cite

Aggregation of the amyloid β protein (Aβ) peptide with 40 or 42 residues is one key feature in Alzheimer's disease (AD). The 1,4-naphthoquinon-2-yl-L-tryptophan (NQTrp) molecule was reported to alter Aβ self-assembly and reduce toxicity. Though nuclear magnetic resonance experiments and various simulations provided atomic information about the interaction of NQTrp with Aβ peptides spanning the regions of residues 12−28 and 17−42, none of these studies were conducted on the fulllength Aβ1−42 peptide. To this end, we performed extensive atomistic replica exchange molecular dynamics simulations of Aβ1−42 dimer with two NQTrp molecules in explicit solvent, by using a force field known to fold diverse proteins correctly. The interactions between NQTrp and Aβ1−42, which change the Aβ interface by reducing most of the intermolecular contacts, are found to be very dynamic and multiple, leading to many transient binding sites. The most favorable binding residues are Arg5, Asp7, Tyr10, His13, Lys16, Lys18, Phe19/Phe20, and Leu34/Met35, providing therefore a completely different picture from in vitro and in silico experiments with NQTrp with shorter Aβ fragments. Importantly, the 10 hot residues that we identified explain the beneficial effect of NQTrp in reducing both the level of Aβ1−42 aggregation and toxicity. Our results also indicate that there is room to design more efficient drugs targeting Aβ1−42 dimer against AD.

show abstract

Section: ■ Methodsmentioning

confidence: 99%

Atomic and Dynamic Insights into the Beneficial Effect of the 1,4-Naphthoquinon-2-yl-l-tryptophan Inhibitor on Alzheimer’s Aβ1–42 Dimer in Terms of Aggregation and Toxicity

Zhang

et al. 2013

ACS Chem. Neurosci.

View full text Add to dashboard Cite

show abstract

“…It can easily interface to other software even quantum chemical packages. The number of replicas and temperature ranges were determined with the aid of a web-protocol (Patriksson and van der Spoel 2008). For Nglycans in explicit solvent, 64 replicas covering the temperature range 300-500 K give an exchange ratio of more than 40 %.…”

Section: Remd Simulations Of N-glycan In Solutionmentioning

confidence: 99%

Conformational flexibility of N-glycans in solution studied by REMD simulations

Nishima

Miyashita³

et al. 2012

Biophys Rev

View full text Add to dashboard Cite

Protein-glycan recognition regulates a wide range of biological and pathogenic processes. Conformational diversity of glycans in solution is apparently incompatible with specific binding to their receptor proteins. One possibility is that among the different conformational states of a glycan, only one conformer is utilized for specific binding to a protein. However, the labile nature of glycans makes characterizing their conformational states a challenging issue. All-atom molecular dynamics (MD) simulations provide the atomic details of glycan structures in solution, but fairly extensive sampling is required for simulating the transitions between rotameric states. This difficulty limits application of conventional MD simulations to small fragments like di-and tri-saccharides. Replica-exchange molecular dynamics (REMD) simulation, with extensive sampling of structures in solution, provides a valuable way to identify a family of glycan conformers. This article reviews recent REMD simulations of glycans carried out by us or other research groups and provides new insights into the conformational equilibria of N-glycans and their alteration by chemical modification. We also emphasize the importance of statistical averaging over the multiple conformers of glycans for comparing simulation results with experimental observables. The results support the concept of "conformer selection" in protein-glycan recognition.

show abstract

“…REMD simulations in this study were started from initial configurations with poses different from the preferred pose as well as from the preferred pose, to demonstrate that a converged equilibrium distribution of poses can be obtained from different initial configurations. We used 14 or 18 replicas in the temperature range of 310-333 K. The temperature increments, with smaller spacing at lower temperatures (e.g., from ΔT 1,2 5 1.2 to ΔT 17,18 5 1.6 in the 18-replica runs), were chosen to ensure homogeneous acceptance ratio between all temperature pairs over the entire temperature range (Patriksson and van der Spoel, 2008). The acceptance ratio was approximately 0.15-0.25.…”

Section: Methodsmentioning

confidence: 99%

A Single Glycine in Extracellular Loop 1 Is the Critical Determinant for Pharmacological Specificity of Dopamine D2 and D3 Receptors

et al. 2013

View full text Add to dashboard Cite

Subtype-selective agents for the dopamine D3 receptor (D3R) have been considered as potential medications for drug addiction and other neuropsychiatric disorders. Medicinal chemistry efforts have led to the discovery of 4-phenylpiperazine derivatives that are .100-fold selective for the dopamine D3 receptor over dopamine D2 receptor (D2R), despite high sequence identity (78% in the transmembrane domain). Based on the recent crystal structure of D3R, we demonstrated that the 4-phenylpiperazine moiety in this class of D3R-selective compounds binds to the conserved orthosteric binding site, whereas the extended aryl amide moiety is oriented toward a divergent secondary binding pocket (SBP). In an effort to further characterize molecular determinants of the selectivity of these compounds, we modeled their binding modes in D3R and D2R by comparative ligand docking and molecular dynamics simulations. We found that the aryl amide moiety in the SBP differentially induces conformational changes in transmembrane segment 2 and extracellular loop 1 (EL1), which amplify the divergence of the SBP in D3R and D2R. Receptor chimera and site-directed mutagenesis studies were used to validate these binding modes and to identify a divergent glycine in EL1 as critical to D3R over D2R subtype selectivity. A better understanding of drug-dependent receptor conformations such as these is key to the rational design of compounds targeting a specific receptor among closely related homologs, and may also lead to discovery of novel chemotypes that exploit subtle differences in protein conformations.

show abstract

A temperature predictor for parallel tempering simulations

Cited by 461 publications

References 43 publications

Atomic and Dynamic Insights into the Beneficial Effect of the 1,4-Naphthoquinon-2-yl-l-tryptophan Inhibitor on Alzheimer’s Aβ1–42 Dimer in Terms of Aggregation and Toxicity

Atomic and Dynamic Insights into the Beneficial Effect of the 1,4-Naphthoquinon-2-yl-l-tryptophan Inhibitor on Alzheimer’s Aβ1–42 Dimer in Terms of Aggregation and Toxicity

Conformational flexibility of N-glycans in solution studied by REMD simulations

A Single Glycine in Extracellular Loop 1 Is the Critical Determinant for Pharmacological Specificity of Dopamine D2 and D3 Receptors

Contact Info

Product

Resources

About