25 research outputs found
Combining Coarse-Grained Protein Models with Replica-Exchange All-Atom Molecular Dynamics
We describe a combination of all-atom simulations with CABS, a
well-established coarse-grained protein modeling tool, into a single multiscale
protocol. The simulation method has been tested on the C-terminal beta hairpin
of protein G, a model system of protein folding. After reconstructing atomistic
details, conformations derived from the CABS simulation were subjected to
replica-exchange molecular dynamics simulations with OPLS-AA and AMBER99sb
force fields in explicit solvent. Such a combination accelerates system
convergence several times in comparison with all-atom simulations starting from
the extended chain conformation, demonstrated by the analysis of melting
curves, the number of native-like conformations as a function of time and
secondary structure propagation. The results strongly suggest that the proposed
multiscale method could be an efficient and accurate tool for high-resolution
studies of protein folding dynamics in larger systems.Comment: 12 pages, 4 figure
Protein mechanical unfolding: importance of non-native interactions
Mechanical unfolding of the fourth domain of Distyostelium discoideum filamin
(DDFLN4) was studied by all-atom molecular dynamics simulations, using the
GROMOS96 force field 43a1 and the simple point charge explicit water solvent.
Our study reveals an important role of non-native interactions in the unfolding
process. Namely, the existence of a peak centered at the end-to-end extension
22 nm in the force-extension curve, is associated with breaking of non-native
hydrogen bonds. Such a peak has been observed in experiments but not in Go
models, where non-native interactions are neglected. We predict that an
additional peak occurs at 2 nm using not only GROMOS96 force field 43a1 but
also Amber 94 and OPLS force fields. This result would stimulate further
experimental studies on elastic properties of DDFLN4.Comment: 27 pages, 15 figure
Role of Resultant Dipole Moment in Mechanical Dissociation of Biological Complexes
Protein-peptide interactions play essential roles in many cellular processes
and their structural characterization is the major focus of current
experimental and theoretical research. Two decades ago, it was proposed to
employ the steered molecular dynamics to assess the strength of protein-peptide
interactions. The idea behind using steered molecular dynamics simulations is
that the mechanical stability can be used as a promising and an efficient
alternative to computationally highly demanding estimation of binding affinity.
However, mechanical stability defined as a peak in force-extension profile
depends on the choice of the pulling direction. Here we propose an uncommon
choice of the pulling direction along resultant dipole moment vector, which has
not been explored in simulations so far. Using explicit solvent all-atom MD
simulations, we apply steered molecular dynamics technique to probe mechanical
resistance of protein-peptide system pulled along two different vectors. A
novel pulling direction, along the resultant dipole moment vector, results in
stronger forces compared to commonly used peptide unbinding along center of
masses vector. Our results demonstrate that resultant dipole moment is one of
the factors influencing the mechanical stability of protein-peptide complex.Comment: 11 pages, 4 figures, 2 table
Universal geometrical factor of protein conformations as a consequence of energy minimization
The biological activity and functional specificity of proteins depend on
their native three-dimensional structures determined by inter- and
intra-molecular interactions. In this paper, we investigate the geometrical
factor of protein conformation as a consequence of energy minimization in
protein folding. Folding simulations of 10 polypeptides with chain length
ranging from 183 to 548 residues manifest that the dimensionless ratio
(V/(A)) of the van der Waals volume V to the surface area A and average
atomic radius of the folded structures, calculated with atomic radii
setting used in SMMP [Eisenmenger F., et. al., Comput. Phys. Commun., 138
(2001) 192], approach 0.49 quickly during the course of energy minimization. A
large scale analysis of protein structures show that the ratio for real and
well-designed proteins is universal and equal to 0.491\pm0.005. The fractional
composition of hydrophobic and hydrophilic residues does not affect the ratio
substantially. The ratio also holds for intrinsically disordered proteins,
while it ceases to be universal for polypeptides with bad folding properties.Comment: 6 pages, 1 table, 4 figure
Folding of the Protein Domain hbSBD
The folding of the alpha-helice domain hbSBD of the mammalian mitochondrial
branched-chain alpha-ketoacid dehydrogenase (BCKD) complex is studied by the
circular dichroism technique in absence of urea. Thermal denaturation is used
to evaluate various thermodynamic parameters defining the equilibrium
unfolding, which is well described by the two-state model with the folding
temperature T_f = 317.8 K and the enthalpy change Delta H_g = 19.67 kcal/mol.
The folding is also studied numerically using the off-lattice coarse-grained Go
model and the Langevin dynamics. The obtained results, including the population
of the native basin, the free energy landscape as a function of the number of
native contacts and the folding kinetics, also suggest that the hbSBD domain is
a two-state folder. These results are consistent with the biological function
of hbSBD in BCKD.Comment: 25 pages, 7 figures, 1 table, published in Biophysical Journa