10,860 research outputs found
The Effect of Box Shape on the Dynamic Properties of Proteins Simulated under Periodic Boundary Conditions
Abstract: The effect of the box shape on the dynamic behavior of proteins simulated under periodic boundary conditions is evaluated. In particular, the influence of simulation boxes defined by the near-densest lattice packing (NDLP) in conjunction with rotational constraints is compared to that of standard box types without these constraints. Three different proteins of varying size, shape, and secondary structure content were examined in the study. The statistical significance of differences in RMSD, radius of gyration, solvent-accessible surface, number of hydrogen bonds, and secondary structure content between proteins, box types, and the application or not of rotational constraints has been assessed. Furthermore, the differences in the collective modes for each protein between different boxes and the application or not of rotational constraints have been examined. In total 105 simulations were performed, and the results compared using a three-way multivariate analysis of variance (MANOVA) for properties derived from the trajectories and a three-way univariate analysis of variance (ANOVA) for collective modes. It is shown that application of roto-translational constraints does not have a statistically significant effect on the results obtained from the different simulations. However, the choice of simulation box was found to have a small (5-10%), but statistically significant effect on the behavior of two of the three proteins included in the study
Computational studies of biomembrane systems: Theoretical considerations, simulation models, and applications
This chapter summarizes several approaches combining theory, simulation and
experiment that aim for a better understanding of phenomena in lipid bilayers
and membrane protein systems, covering topics such as lipid rafts, membrane
mediated interactions, attraction between transmembrane proteins, and
aggregation in biomembranes leading to large superstructures such as the light
harvesting complex of green plants. After a general overview of theoretical
considerations and continuum theory of lipid membranes we introduce different
options for simulations of biomembrane systems, addressing questions such as:
What can be learned from generic models? When is it expedient to go beyond
them? And what are the merits and challenges for systematic coarse graining and
quasi-atomistic coarse grained models that ensure a certain chemical
specificity
Dynamics of protein-protein encounter: a Langevin equation approach with reaction patches
We study the formation of protein-protein encounter complexes with a Langevin
equation approach that considers direct, steric and thermal forces. As three
model systems with distinctly different properties we consider the pairs
barnase:barstar, cytochrome c:cytochrome c peroxidase and p53:MDM2. In each
case, proteins are modeled either as spherical particles, as dipolar spheres or
as collection of several small beads with one dipole. Spherical reaction
patches are placed on the model proteins according to the known experimental
structures of the protein complexes. In the computer simulations, concentration
is varied by changing box size. Encounter is defined as overlap of the reaction
patches and the corresponding first passage times are recorded together with
the number of unsuccessful contacts before encounter. We find that encounter
frequency scales linearly with protein concentration, thus proving that our
microscopic model results in a well-defined macroscopic encounter rate. The
number of unsuccessful contacts before encounter decreases with increasing
encounter rate and ranges from 20-9000. For all three models, encounter rates
are obtained within one order of magnitude of the experimentally measured
association rates. Electrostatic steering enhances association up to 50-fold.
If diffusional encounter is dominant (p53:MDM2) or similarly important as
electrostatic steering (barnase:barstar), then encounter rate decreases with
decreasing patch radius. More detailed modeling of protein shapes decreases
encounter rates by 5-95 percent. Our study shows how generic principles of
protein-protein association are modulated by molecular features of the systems
under consideration. Moreover it allows us to assess different coarse-graining
strategies for the future modelling of the dynamics of large protein complexes
DynamO: A free O(N) general event-driven molecular-dynamics simulator
Molecular-dynamics algorithms for systems of particles interacting through
discrete or "hard" potentials are fundamentally different to the methods for
continuous or "soft" potential systems. Although many software packages have
been developed for continuous potential systems, software for discrete
potential systems based on event-driven algorithms are relatively scarce and
specialized. We present DynamO, a general event-driven simulation package which
displays the optimal O(N) asymptotic scaling of the computational cost with the
number of particles N, rather than the O(N log(N)) scaling found in most
standard algorithms. DynamO provides reference implementations of the best
available event-driven algorithms. These techniques allow the rapid simulation
of both complex and large (>10^6 particles) systems for long times. The
performance of the program is benchmarked for elastic hard sphere systems,
homogeneous cooling and sheared inelastic hard spheres, and equilibrium
Lennard-Jones fluids. This software and its documentation are distributed under
the GNU General Public license and can be freely downloaded from
http://marcusbannerman.co.uk/dynamo
New insight into cataract formation -- enhanced stability through mutual attraction
Small-angle neutron scattering experiments and molecular dynamics simulations
combined with an application of concepts from soft matter physics to complex
protein mixtures provide new insight into the stability of eye lens protein
mixtures. Exploring this colloid-protein analogy we demonstrate that weak
attractions between unlike proteins help to maintain lens transparency in an
extremely sensitive and non-monotonic manner. These results not only represent
an important step towards a better understanding of protein condensation
diseases such as cataract formation, but provide general guidelines for tuning
the stability of colloid mixtures, a topic relevant for soft matter physics and
industrial applications.Comment: 4 pages, 4 figures. Accepted for publication on Phys. Rev. Let
IMAGE CHARGE SOLVATION MODEL (ICSM) FOR SIMULATING BIOMOLECULES AND KCSA ION-CHANNELS
We present an order N method for calculating electrostatic interactions that has been integrated into the molecular dynamics portion of the TINKER Molecular Modeling package. This method, termed the Image-Charge Solvation Model (ICSM), and introduced previously by Dr. Lin et al. (1) in 2009, is a hybrid electrostatic approach that combines the strengths of both explicit and implicit representations of the solvent. In this model, a multiple-image method is used to calculate reaction fields due to the implicit solvent while the Fast Multipole Method (FMM) is used to calculate the Coulomb interactions for all charges, including the charges in the explicit solvent part.
The integrated package is validated through simulations of liquid water. The results are compared with those obtained by the Particle Mesh Ewald (PME) method that is built in the TINKER package. Timing performance of TINKER with the integrated ICSM is benchmarked on bulk water as a function of the size of the system. In particular, timing analysis results show that the ICSM outperforms the PME for sufficiently large systems with the break-even point at around 30,000 particles in the simulated system. To demonstrate the capability of the package on large macromolecules, the model is used to simulate the potassium channel KcsA
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