Observation of “Ionic Lock” Formation in Molecular Dynamics Simulations of Wild-Type β1and β2Adrenergic Receptors

Biochemistry ◽  
2009 ◽  
Vol 48 (22) ◽  
pp. 4789-4797 ◽  
Author(s):  
Stefano Vanni ◽  
Marilisa Neri ◽  
Ivano Tavernelli ◽  
Ursula Rothlisberger
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Wild Type ◽  
Dynamics Simulations

scholarly journals Exploration of the cofactor specificity of wild-type phosphite dehydrogenase and its mutant using molecular dynamics simulations

RSC Advances ◽  
2021 ◽  
Vol 11 (24) ◽  
pp. 14527-14533
Author(s):  
Kunlu Liu ◽  
Min Wang ◽  
Yubo Zhou ◽  
Hongxiang Wang ◽  
Yudong Liu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Wild Type ◽  
Cofactor Specificity ◽  
Phosphite Dehydrogenase ◽  
Dynamics Simulations

Phosphite dehydrogenase (Pdh) catalyzes the NAD-dependent oxidation of phosphite to phosphate with the formation of NADH.

scholarly journals Insights into the Folding and Unfolding Processes of Wild-Type and Mutated SH3 Domain by Molecular Dynamics and Replica Exchange Molecular Dynamics Simulations

PLoS ONE ◽  
2013 ◽  
Vol 8 (5) ◽  
pp. e64886 ◽  
Author(s):  
Wen-Ting Chu ◽  
Ji-Long Zhang ◽  
Qing-Chuan Zheng ◽  
Lin Chen ◽  
Hong-Xing Zhang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Sh3 Domain ◽  
Replica Exchange ◽  
Wild Type ◽  
Replica Exchange Molecular Dynamics ◽  
Dynamics Simulations

scholarly journals Allosteric Communication within the Cytoplasmic Region of the Histidine Kinase CpxA, Revealed by Molecular Dynamics Simulations of the Wild-Type and M228V Proteins

2015 ◽  
Vol 108 (2) ◽  
pp. 184a
Author(s):  
Marlet Martinez ◽  
Nathalie Duclert ◽  
Jean-Michel Betton ◽  
Pedro M. Alzari ◽  
Michael Nilges ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Histidine Kinase ◽  
Wild Type ◽  
Cytoplasmic Region ◽  
Allosteric Communication ◽  
Dynamics Simulations

scholarly journals Molecular dynamics simulations of the interaction of wild type and mutant human CYP2J2 with polyunsaturated fatty acids

2019 ◽  
Vol 12 (1) ◽  
Author(s):  
K. K. Abelak ◽  
D. Bishop-Bailey ◽  
I. Nobeli
Keyword(s):  
Molecular Dynamics ◽  
Arachidonic Acid ◽  
Molecular Dynamics Simulations ◽  
Molecular Mechanisms ◽  
Homology Model ◽  
Cytochrome P450 Enzyme ◽  
Wild Type ◽  
Substrate Preferences ◽  
P450 Enzyme ◽  
Dynamics Simulations

Abstract Objectives The data presented here is part of a study that was aimed at characterizing the molecular mechanisms of polyunsaturated fatty acid metabolism by CYP2J2, the main cytochrome P450 enzyme active in the human cardiovasculature. This part comprises the molecular dynamics simulations of the binding of three eicosanoid substrates to wild type and mutant forms of the enzyme. These simulations were carried out with the aim of dissecting the importance of individual residues in the active site and the roles they might play in dictating the binding and catalytic specificity exhibited by CYP2J2. Data description The data comprise: (a) a new homology model of CYP2J2, (b) a number of predicted low-energy complexes of CYP2J2 with arachidonic acid, docosahexaenoic acid and eicosapentaenoic acid, produced with molecular docking and (c) a series of molecular dynamics simulations of the wild type and four mutants interacting with arachidonic acid as well as simulations of the wild type interacting with the two other eicosanoid ligands. The simulations may be helpful in identifying the determinants of substrate specificity of this enzyme and in unraveling the role of individual mutations on its function. They may also help guide the generation of mutants with altered substrate preferences.

scholarly journals Interaction of a sarcolipin pentamer and monomer with the sarcoplasmic reticulum calcium pump, SERCA

2019 ◽  
Author(s):  
J. P. Glaves ◽  
J. O. Primeau ◽  
P. A. Gorski ◽  
L. M. Espinoza-Fonseca ◽  
M. J. Lemieux ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Sarcoplasmic Reticulum ◽  
Molecular Dynamics Simulations ◽  
Maximal Activity ◽  
Protein Docking ◽  
The Novel ◽  
Wild Type ◽  
Transmembrane Segment ◽  
Dynamics Simulations ◽  
Sarcoplasmic Reticulum Calcium

ABSTRACTThe sequential rise and fall of cytosolic calcium underlies the contraction-relaxation cycle of muscle cells. While contraction is initiated by the release of calcium from the sarcoplasmic reticulum, muscle relaxation involves the active transport of calcium back into the sarcoplasmic reticulum. This re-uptake of calcium is catalysed by the sarco-endoplasmic reticulum Ca2+-ATPase (SERCA), which plays a lead role in muscle contractility. The activity of SERCA is regulated by small membrane protein subunits, most well-known being phospholamban (PLN) and sarcolipin (SLN). SLN physically interacts with SERCA and differentially regulates contractility in skeletal and atrial muscle. SLN has also been implicated in skeletal muscle thermogenesis. Despite these important roles, the structural mechanisms by which SLN modulates SERCA-dependent contractility and thermogenesis remain unclear. Here, we functionally characterized wild-type SLN and a pair of mutants, Asn4-Ala and Thr5-Ala, which yielded gain-of-function behavior comparable to what has been found for PLN. Next, we analyzed twodimensional crystals of SERCA in the presence of wild-type SLN by electron cryo-microscopy. The fundamental units of the crystals are anti-parallel dimer ribbons of SERCA, known for decades as an assembly of calcium-free SERCA molecules induced by the addition of decavanadate. A projection map of the SERCA-SLN complex was determined to a resolution of 8.5 Å, which allowed the direct visualization of a SLN pentamer. The SLN pentamer was found to interact with transmembrane segment M3 of SERCA, though the interaction appeared to be indirect and mediated by an additional density consistent with a SLN monomer. This SERCA-SLN complex correlated with the ability of SLN to decrease the maximal activity of SERCA, which is distinct from the ability of PLN to increase the maximal activity of SLN. Protein-protein docking and molecular dynamics simulations provided models for the SLN pentamer and the novel interaction between SERCA and a SLN monomer.STATEMENT OF SIGNIFICANCEThis research article describes a novel complex of the sarcoplasmic reticulum calcium pump SERCA and its regulatory subunit sarcolipin. Given the potential role of sarcolipin in skeletal muscle non-shivering thermogenesis, the interactions between SERCA and sarcolipin are of critical importance. Using complementary approaches of functional analysis, electron crystallography, and molecular dynamics simulations, we demonstrate an inherent interaction between SERCA, a sarcolipin monomer, and a sarcolipin pentamer. The interaction involves transmembrane segment M3 of SERCA, which allows sarcolipin to decrease the maximal activity or turnover rate of SERCA. Protein-protein docking and molecular dynamics simulations provided models for the SLN pentamer and the novel interaction between SERCA and a SLN monomer.

scholarly journals Molecular Dynamics Simulations Suggest a Non-Doublet Decoding Model of –1 Frameshifting by tRNASer3

Biomolecules ◽  
2019 ◽  
Vol 9 (11) ◽  
pp. 745 ◽  
Author(s):  
Caulfield ◽  
Coban ◽  
Tek ◽  
Flores
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bond ◽  
Molecular Dynamics Simulations ◽  
Wild Type ◽  
E Coli ◽  
The Third ◽  
Dynamics Simulations

In-frame decoding in the ribosome occurs through canonical or wobble Watson–Crick pairing of three mRNA codon bases (a triplet) with a triplet of anticodon bases in tRNA. Departures from the triplet–triplet interaction can result in frameshifting, meaning downstream mRNA codons are then read in a different register. There are many mechanisms to induce frameshifting, and most are insufficiently understood. One previously proposed mechanism is doublet decoding, in which only codon bases 1 and 2 are read by anticodon bases 34 and 35, which would lead to –1 frameshifting. In E. coli, tRNASer3GCU can induce –1 frameshifting at alanine (GCA) codons. The logic of the doublet decoding model is that the Ala codon’s GC could pair with the tRNASer3′s GC, leaving the third anticodon residue U36 making no interactions with mRNA. Under that model, a U36C mutation would still induce –1 frameshifting, but experiments refute this. We perform all-atom simulations of wild-type tRNASer3, as well as a U36C mutant. Our simulations revealed a hydrogen bond between U36 of the anticodon and G1 of the codon. The U36C mutant cannot make this interaction, as it lacks the hydrogen-bond-donating H3. The simulation thus suggests a novel, non-doublet decoding mechanism for −1 frameshifting by tRNASer3 at Ala codons.

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