Packing optimization for automated generation of complex system's initial configurations for molecular dynamics and docking

Martínez, José Mário; Martı́nez, Leandro

doi:10.1002/jcc.10216

Cited by 576 publications

(391 citation statements)

References 25 publications

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“…The structures of TRR and TR bound to Triac were recently obtained by our research group and were refined to 2.0 and 2.5 Å, respectively. 26 The complete simulated systems were built with Packmol, 40,41 containing the LBD of either subtype, water, and one counterion for each charged residue for electroneutrality: 43 Na + and 30 Cl -ions for TRR and 43 Na + and 30 Cl -for TR bound to Triac. For the apo-structures of both LBD subtypes there is one less Na + in solution.…”

Section: Methodsmentioning

confidence: 99%

On the Denaturation Mechanisms of the Ligand Binding Domain of Thyroid Hormone Receptors

et al. 2009

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The ligand binding domain (LBD) of nuclear hormone receptors adopts a very compact, mostly R-helical structure that binds specific ligands with very high affinity. We use circular dichroism spectroscopy and high-temperature molecular dynamics simulations to investigate unfolding of the LBDs of thyroid hormone receptors (TRs). A molecular description of the denaturation mechanisms is obtained by molecular dynamics simulations of the TRR and TR LBDs in the absence and in the presence of the natural ligand Triac. The simulations show that the thermal unfolding of the LBD starts with the loss of native contacts and secondary structure elements, while the structure remains essentially compact, resembling a molten globule state. This differs from most protein denaturation simulations reported to date and suggests that the folding mechanism may start with the hydrophobic collapse of the TR LBDs. Our results reveal that the stabilities of the LBDs of the TRR and TR subtypes are affected to different degrees by the binding of the isoform selective ligand Triac and that ligand binding confers protection against thermal denaturation and unfolding in a subtype specific manner. Our simulations indicate two mechanisms by which the ligand stabilizes the LBD: (1) by enhancing the interactions between H8 and H11, and the interaction of the region between H1 and the Ω-loop with the core of the LBD, and (2) by shielding the hydrophobic H6 from hydration.

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Section: Methodsmentioning

confidence: 99%

On the Denaturation Mechanisms of the Ligand Binding Domain of Thyroid Hormone Receptors

et al. 2009

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“…On the other hand, by minimizing the packing function and recognizing a global solution with f = 0 one is sure that there are no clashes, and energy minimization and/or simulations may run smoothly (even if the total energy of the system is not satisfactory and needs to be equilibrated to the thermodynamic energy at the desired temperature). 1 The smoothness of the objective function facilitates the minimization procedure to the point that global solutions are obtained frequently. At the same time, the objective function can be evaluated using very fast procedures due to its local character (there are no long-range interactions), as will be described below.…”

Section: Mathematical Modelmentioning

confidence: 99%

“…Frequently, the instability and nondifferentiability of the potential energy resulting from overlapping atoms is hard to overcome. 1 For a simple system such as a water box, we can obtain an adequate configuration simply by ordering the molecules in a regular lattice. However, for slightly more complex systems such as a solvated peptide, regular configurations would almost certainly contain overlapping atoms.…”

Section: Introductionmentioning

confidence: 99%

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PACKMOL: A package for building initial configurations for molecular dynamics simulations

et al. 2009

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Abstract:Adequate initial configurations for molecular dynamics simulations consist of arrangements of molecules distributed in space in such a way to approximately represent the system's overall structure. In order that the simulations are not disrupted by large van der Waals repulsive interactions, atoms from different molecules must keep safe pairwise distances. Obtaining such a molecular arrangement can be considered a packing problem: Each type molecule must satisfy spatial constraints related to the geometry of the system, and the distance between atoms of different molecules must be greater than some specified tolerance. We have developed a code able to pack millions of atoms, grouped in arbitrarily complex molecules, inside a variety of three-dimensional regions. The regions may be intersections of spheres, ellipses, cylinders, planes, or boxes. The user must provide only the structure of one molecule of each type and the geometrical constraints that each type of molecule must satisfy. Building complex mixtures, interfaces, solvating biomolecules in water, other solvents, or mixtures of solvents, is straightforward. In addition, different atoms belonging to the same molecule may also be restricted to different spatial regions, in such a way that more ordered molecular arrangements can be built, as micelles, lipid double-layers, etc. The packing time for state-of-the-art molecular dynamics systems varies from a few seconds to a few minutes in a personal computer. The input files are simple and currently compatible with PDB, Tinker, Molden, or Moldy coordinate files. The package is distributed as free software and can be downloaded from

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“…The temperatures studied were 300, 250, 210, 180, 170 and 155 K for the 0.768 g cm −3 isochore and 300, 250, 210, 180 and 170 K for the 0.878 g cm −3 isochore. The initial configuration for the molecular dynamics simulations at 300 K was generated using the PACKMOL program [34]. The system was then slowly cooled to obtain lower temperatures.…”

Section: Molecular Dynamicsmentioning

confidence: 99%

Multiple Time Scale Behaviors and Network Dynamics in Liquid Methanol

2008

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Canonical ensemble molecular dynamics simulations of liquid methanol, modeled using a rigidbody, pair-additive potential, are used to compute static distributions and temporal correlations of tagged molecule potential energies as a means of characterising the liquid state dynamics. The static distribution of tagged molecule potential energies shows a clear multimodal structure with three distinct peaks, similar to those observed previously in water and liquid silica. The multimodality is shown to originate from electrostatic effects, but not from local, hydrogen-bond interactions. An interesting outcome of this study is the remarkable similarity in the tagged potential energy power spectra of methanol, water and silica, despite the differences in the underlying interactions and the dimensionality of the network. All three liquids show a distinct multiple time scale (MTS) regime with a 1/f α dependence with a clear positive correlation between the scaling exponent α and the diffusivity. The low-frequency limit of the MTS regime is determined by the frequency of crossover to white noise behaviour which occurs at approximately 0.1 cm −1 in the case of methanol under standard temperature and pressure conditions. The power spectral regime above 200 cm −1 in all three systems is dominated by resonances due to localised vibrations, such as librations. The correlation between α and the diffusivity in all three liquids appears to be related to the strength of the coupling between the localised motions and the larger length/time-scale network reorganizations. Thus the time scales associated with network reorganization dynamics appear to be qualitatively similar in these systems, despite the fact that water and silica both display diffusional anomalies but methanol does not.

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Packing optimization for automated generation of complex system's initial configurations for molecular dynamics and docking

Cited by 576 publications

References 25 publications

On the Denaturation Mechanisms of the Ligand Binding Domain of Thyroid Hormone Receptors

On the Denaturation Mechanisms of the Ligand Binding Domain of Thyroid Hormone Receptors

PACKMOL: A package for building initial configurations for molecular dynamics simulations

Multiple Time Scale Behaviors and Network Dynamics in Liquid Methanol

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