Molecular Dynamics Machine: Special-Purpose Computer for Molecular Dynamics Simulations

Narumi, Takatsune; Susukita, Ryutaro; Ebisuzaki, Toshikazu; Mcniven, Geoffrey; Elmegreen, Bruce G.

doi:10.1080/08927029908022078

Cited by 74 publications

(42 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The MDGRAPE-2 is a single board which plugs into the PCI bus of a general purpose computer, and is designed for extremely fast calculation of forces and potentials in molecular dynamics simulations [24]. It is the third generation of such hardware, which evolved from the work of J. Makino et al at the University of Tokyo on similar hardware called the GRAPE (for GRAvity PipE), for doing gravitational Nbody problems [25].…”

Section: Appendix: Mdgrapementioning

confidence: 99%

Nonuniform neutron-rich matter and coherent neutrino scattering

et al. 2004

View full text Add to dashboard Cite

Nonuniform neutron-rich matter present in both core-collapse supernovae and neutron-star crusts is described in terms of a semiclassical model that reproduces nuclear-matter properties and includes long-range Coulomb interactions. The neutron-neutron correlation function and the corresponding static structure factor are calculated from molecular dynamics simulations involving 40,000 to 100,000 nucleons. The static structure factor describes coherent neutrino scattering which is expected to dominate the neutrino opacity. At low momentum transfers the static structure factor is found to be small because of ion screening. In contrast, at intermediate momentum transfers the static structure factor displays a large peak due to coherent scattering from all the neutrons in a cluster. This peak moves to higher momentum transfers and decreases in amplitude as the density increases. A large static structure factor at zero momentum transfer, indicative of large density fluctuations during a first-order phase transition, may increase the neutrino opacity. However, no evidence of such an increase has been found. Therefore, it is unlikely that the system undergoes a simple first-order phase transition. Further, to compare our results to more conventional approaches, a cluster algorithm is introduced to determine the composition of the clusters in our simulations. Neutrino opacities are then calculated within a single heavy nucleus approximation as is done in most current supernova simulations. It is found that corrections to the single heavy nucleus approximation first appear at a density of the order of 10 13 g/cm 3 and increase rapidly with increasing density. Thus, neutrino opacities are overestimated in the single heavy nucleus approximation relative to the complete molecular dynamics simulations.

show abstract

Section: Appendix: Mdgrapementioning

confidence: 99%

Nonuniform neutron-rich matter and coherent neutrino scattering

et al. 2004

View full text Add to dashboard Cite

show abstract

“…All MD simulations were carried out using modified Amber 6.0 (43) for MDM on a PC (Intel Pentium4, 2.53 GHz) equipped with an MDGrape-2 board, which is a main component of the MDM (4 chips; 64 Gflops) (35). The parm96 force field (44) was adopted, and the time step was set at 1 fs.…”

Section: Equilibrationmentioning

confidence: 99%

Novel Mechanism of Interaction of p85 Subunit of Phosphatidylinositol 3-Kinase and ErbB3 Receptor-derived Phosphotyrosyl Peptides

Suenaga

Tsuji

Hatakeyama

et al. 2005

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Ligand-activated and tyrosine-phosphorylated ErbB3 receptor binds to the SH2 domain of the p85 subunit of phosphatidylinositol 3-kinase and initiates intracellular signaling. Here, we studied the interactions between the N-(N-SH2) and C-(C-SH2) terminal SH2 domains of the p85 subunit of the phosphatidylinositol 3-kinase and eight ErbB3 receptor-derived phosphotyrosyl peptides (P-peptides) by using molecular dynamics, free energy, and surface plasmon resonance (SPR) analyses. In SPR analysis, these P-peptides showed no binding to the C-SH2 domain, but P-peptides containing a phospho-YXXM or a non-phospho-YXXM motif did bind to the N-SH2 domain. The N-SH2 domain has two phosphotyrosine binding sites in its N-(N1) and C-(N2) terminal regions. Interestingly, we found that P-peptides of pY1180 and pY1241 favored to bind to the N2 site, although all other P-peptides showed favorable binding to the N1 site. Remarkably, two phosphotyrosines, pY1178 and pY1243, which are just 63 amino acids apart from the pY1241 and pY1180, respectively, showed favorable binding to the N1 site. These findings indicate a possibility that the pair of phosphotyrosines, pY1178-pY1241 or pY1243-pY1180, will fold into an appropriate configuration for binding to the N1 and N2 sites simultaneously. Our model structures of the cytoplasmic C-terminal domain of ErbB3 receptor also strongly supported the speculation. The calculated binding free energies between the N-SH2 domain and P-peptides showed excellent qualitative agreement with SPR data with a correlation coefficient of 0.91. The total electrostatic solvation energy between the N-SH2 domain and P-peptide was the dominant factor for its binding affinity.Overexpression or mutation of ErbB receptors (ErbB1; epidermal growth factor receptor, ErbB2; Neu, ErbB3, and ErbB4) is implicated as a cause of various human cancers (1-4). ErbB3 is a kinase-impaired receptor; nevertheless ligand binding to the receptor can cause heterodimerization with another ErbB receptor and induces activation and transphosphorylation of the ErbB3 receptor in cells (5-7). Once activated and tyrosinephosphorylated, the ErbB3 binds to the Src homology 2 (SH2) 1 domain of p85 (a regulatory subunit of phosphatidylinositol 3-kinase (PI3K)) at its binding sites within the C-terminal regulatory region. Six binding sites have been identified for p85 binding; accordingly the ErbB3 receptor is considered as a scaffold protein for PI3K (2, 4, 8 -9). Studies on insulin receptor substrate-1 (IRS-1) (10 -12), platelet-derived growth factor receptor (13), and ErbB receptors (4, 8) revealed that the phospho-YXXM (pYXXM) motif is a specific binding site for SH2 domain of the p85, to which binding is necessary for activation of the p110 catalytic subunit of PI3K (12,14). On the other hand, the p85 is reported to bind to a pYVXV motif in the hepatocyte growth factor receptor (15), and another study also suggested that there was no binding specificity in any binding motifs for SH2 domains of p85, PLC␥, RasGAP, and Shc (16).The p85 has a tand...

show abstract

“…9), which is the main component of the MDM. Parm96, which is a parameter set for molecular mechanical force fields used for simulations of biomolecules (22), was adopted and the time step was set at 1 fs.…”

Section: Methodsmentioning

confidence: 99%

Tyr-317 Phosphorylation Increases Shc Structural Rigidity and Reduces Coupling of Domain Motions Remote from the Phosphorylation Site as Revealed by Molecular Dynamics Simulations

Suenaga

Kiyatkin

Hatakeyama

et al. 2004

Journal of Biological Chemistry

Self Cite

View full text Add to dashboard Cite

Activated receptor tyrosine kinases bind the Shc adaptor protein through its N-terminal phosphotyrosine-binding (PTB) and C-terminal Src homology 2 (SH2) domains. After binding, Shc is phosphorylated within the central collagen-homology (CH) linker regionon Tyr-317, a residue remote to both the PTB and SH2 domains. Shc phosphorylation plays a pivotal role in the initiation of mitogenic signaling through the Ras/Raf/ MEK/ERK pathway, but it is unclear if Tyr-317 phosphorylation affects Shc-receptor interactions through the PTB and SH2 domains. To investigate the structural impact of Shc phosphorylation, molecular dynamics simulations were carried out using special-purpose Molecular Dynamics Machine-Grape computers. After a 1-nanosecond equilibration, atomic motions in the structures of unphosphorylated Shc and Shc phosphorylated on Tyr-317 were calculated during a 2-nanosecond period. The results reveal larger phosphotyrosine-binding domain fluctuations and more structural flexibility of unphosphorylated Shc compared with phosphorylated Shc. Collective motions between the PTB-SH2, PTB-CH, and CH-SH2 domains were highly correlated only in unphosphorylated Shc. Dramatic changes in domain coupling and structural rigidity, induced by Tyr-317 phosphorylation, may alter Shc function, bringing about marked differences in the association of unphosphorylated and phosphorylated Shc with its numerous partners, including activated membrane receptors.The Src homology and collagen domain protein (Shc) 1 is an adaptor protein that plays a pivotal role in the signal transfer from receptor tyrosine kinases (RTK) to downstream signaling pathways regulating cell survival, proliferation, and differentiation (1). After ligand-induced autophosphorylation, RTKs bind and phosphorylate Shc on selected tyrosine residues. The Shc protein consists of an amino-terminal phosphotyrosinebinding (PTB) domain, a central collagen-homology (CH) region, which contains the major site of tyrosine phosphorylation at Tyr-317 and a carboxyl-terminal Src homology 2 (SH2) domain (2). Phosphorylation of Tyr-317 results in the formation of a docking site for other signaling proteins, e.g. growth factor receptor binding protein 2 (Grb2).Current paradigms for signal transduction emphasize that large adaptor proteins, such as Shc, are organized as "beads on a string." A single bead is a domain, ranging in size from 50 to 120 amino acids; they are responsible for particular interactions with other proteins or phospholipids (3). A signaling protein containing several domains can simultaneously associate with two or more binding partners. For example, an adaptor protein can bind to RTKs using an SH2 or PTB domain and associate with a signaling partner by means of another domain. It may appear at first that the modular structure underlying signaling interactions implies that the phosphorylation of residues located outside specialized binding domains should not affect the structural flexibility and intramolecular motions of these domains. Consequently, it should n...

show abstract

Molecular Dynamics Machine: Special-Purpose Computer for Molecular Dynamics Simulations

Cited by 74 publications

References 8 publications

Nonuniform neutron-rich matter and coherent neutrino scattering

Nonuniform neutron-rich matter and coherent neutrino scattering

Novel Mechanism of Interaction of p85 Subunit of Phosphatidylinositol 3-Kinase and ErbB3 Receptor-derived Phosphotyrosyl Peptides

Tyr-317 Phosphorylation Increases Shc Structural Rigidity and Reduces Coupling of Domain Motions Remote from the Phosphorylation Site as Revealed by Molecular Dynamics Simulations

Contact Info

Product

Resources

About