Comparison of Continuum and Explicit Models of Solvation:  Potentials of Mean Force for Alanine Dipeptide

1996 ◽  
Vol 100 (5) ◽  
pp. 1439-1441 ◽  
Author(s):  
Tami J. Marrone ◽  
Michael K. Gilson ◽  
J. Andrew McCammon
Keyword(s):  
Potentials Of Mean Force ◽  
Alanine Dipeptide

Potentials of mean force for biomolecular simulations: Theory and test on alanine dipeptide

1996 ◽  
Vol 104 (21) ◽  
pp. 8639-8648 ◽  
Author(s):  
Matteo Pellegrini ◽  
Niels Gro/nbech‐Jensen ◽  
Sebastian Doniach
Keyword(s):  
Potentials Of Mean Force ◽  
Biomolecular Simulations ◽  
Alanine Dipeptide

scholarly journals Atomistic Analysis of ToxN and ToxI Complex Unbinding Mechanism

2018 ◽  
Vol 19 (11) ◽  
pp. 3524 ◽  
Author(s):  
Guodong Hu ◽  
Xiu Yu ◽  
Yunqiang Bian ◽  
Zanxia Cao ◽  
Shicai Xu ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Noncoding Rna ◽  
Md Simulations ◽  
Normal Function ◽  
Toxin Complex ◽  
Potentials Of Mean Force ◽  
Protein Toxins ◽  
Function Relationship ◽  
The Stability ◽  
Smd Simulations

ToxIN is a triangular structure formed by three protein toxins (ToxNs) and three specific noncoding RNA antitoxins (ToxIs). To respond to stimuli, ToxI is preferentially degraded, releasing the ToxN. Thus, the dynamic character is essential in the normal function interactions between ToxN and ToxI. Here, equilibrated molecular dynamics (MD) simulations were performed to study the stability of ToxN and ToxI. The results indicate that ToxI adjusts the conformation of 3′ and 5′ termini to bind to ToxN. Steered molecular dynamics (SMD) simulations combined with the recently developed thermodynamic integration in 3nD (TI3nD) method were carried out to investigate ToxN unbinding from the ToxIN complex. The potentials of mean force (PMFs) and atomistic pictures suggest the unbinding mechanism as follows: (1) dissociation of the 5′ terminus from ToxN, (2) missing the interactions involved in the 3′ terminus of ToxI without three nucleotides (G31, A32, and A33), (3) starting to unfold for ToxI, (4) leaving the binding package of ToxN for three nucleotides of ToxI, (5) unfolding of ToxI. This work provides information on the structure-function relationship at the atomistic level, which is helpful for designing new potent antibacterial drugs in the future.

scholarly journals Multi-Scale Modeling of Aqueous-Phase Methane Diffusion in Silicate Channels

2021 ◽  
Author(s):  
Tom Pace ◽  
Hadi Rahmaninejad ◽  
Bin Sun ◽  
Peter Kekenes-Huskey
Keyword(s):  
Molecular Dynamics ◽  
Multi Scale ◽  
Relative Contribution ◽  
Kinetic Information ◽  
Two Factors ◽  
Molecule Transport ◽  
Potentials Of Mean Force ◽  
Methane Diffusion ◽  
Dynamics Simulations ◽  
Small Molecule Transport

Silica-based materials including zeolites are commonly used for wide ranging applications including separations and catalysis.<br>Substrate transport rates in these materials often significantly influence the efficiency of such applications.<br>Two factors that contribute to transport rates include<br>1) the porosity of the silicate matrix and<br>2) non-bonding interactions between the diffusing species and the silicate surface.<br>Here, we utilize computer simulation to resolve the relative contribution of these factors to effective methane transport rates in a silicate channel.<br>Specifically, we develop a `homogenized' model of methane transport valid at micron and longer length scales that incorporates atomistic-scale kinetic information.<br>The atomistic-scale data are obtained from extensive molecular dynamics simulations that yield local diffusion coefficients and potentials of mean force.<br>With this model, we demonstrate how nuances in silicate hydration and silica/methane interactions impact 'macroscale' methane diffusion rates in bulk silicate materials.<br>This hybrid homogenization/molecular dynamics approach will be of general use for describing small molecule transport in materials with detailed molecular interactions.<br><br>

scholarly journals Structure of theMycobacterium tuberculosisd-Alanine:d-Alanine Ligase, a Target of the Antituberculosis Drug d-Cycloserine

2010 ◽  
Vol 55 (1) ◽  
pp. 291-301 ◽  
Author(s):  
John B. Bruning ◽  
Ana C. Murillo ◽  
Ofelia Chacon ◽  
Raúl G. Barletta ◽  
James C. Sacchettini
Keyword(s):  
Crystal Structure ◽  
Binding Site ◽  
Kinetic Studies ◽  
Structural Rearrangement ◽  
Peptidoglycan Biosynthesis ◽  
Binding Cavity ◽  
Binding Pockets ◽  
Loop Regions ◽  
Discrete Domains ◽  
Alanine Dipeptide

ABSTRACTd-Alanine:d-alanine ligase (EC 6.3.2.4; Ddl) catalyzes the ATP-driven ligation of twod-alanine (d-Ala) molecules to form thed-alanyl:d-alanine dipeptide. This molecule is a key building block in peptidoglycan biosynthesis, making Ddl an attractive target for drug development.d-Cycloserine (DCS), an analog ofd-Ala and a prototype Ddl inhibitor, has shown promise for the treatment of tuberculosis. Here, we report the crystal structure ofMycobacterium tuberculosisDdl at a resolution of 2.1 Å. This structure indicates that Ddl is a dimer and consists of three discrete domains; the ligand binding cavity is at the intersection of all three domains and conjoined by several loop regions. TheM. tuberculosisapo Ddl structure shows a novel conformation that has not yet been observed in Ddl enzymes from other species. The nucleotide andd-alanine binding pockets are flexible, requiring significant structural rearrangement of the bordering regions for entry and binding of both ATP andd-Ala molecules. Solution affinity and kinetic studies showed that DCS interacts with Ddl in a manner similar to that observed ford-Ala. Each ligand binds to two binding sites that have significant differences in affinity, with the first binding site exhibiting high affinity. DCS inhibits the enzyme, with a 50% inhibitory concentration (IC50) of 0.37 mM under standard assay conditions, implicating a preferential and weak inhibition at the second, lower-affinity binding site. Moreover, DCS binding is tighter at higher ATP concentrations. The crystal structure illustrates potential drugable sites that may result in the development of more-effective Ddl inhibitors.

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