282 research outputs found
Recoverable One-dimensional Encoding of Three-dimensional Protein Structures
Protein one-dimensional (1D) structures such as secondary structure and
contact number provide intuitive pictures to understand how the native
three-dimensional (3D) structure of a protein is encoded in the amino acid
sequence. However, it has not been clear whether a given set of 1D structures
contains sufficient information for recovering the underlying 3D structure.
Here we show that the 3D structure of a protein can be recovered from a set of
three types of 1D structures, namely, secondary structure, contact number and
residue-wise contact order which is introduced here for the first time. Using
simulated annealing molecular dynamics simulations, the structures satisfying
the given native 1D structural restraints were sought for 16 proteins of
various structural classes and of sizes ranging from 56 to 146 residues. By
selecting the structures best satisfying the restraints, all the proteins
showed a coordinate RMS deviation of less than 4\AA{} from the native
structure, and for most of them, the deviation was even less than 2\AA{}. The
present result opens a new possibility to protein structure prediction and our
understanding of the sequence-structure relationship.Comment: Corrected title. No Change In Content
Allosterically Tunable, DNA-Based Switches Triggered by Heavy Metals
Here we demonstrate the rational design of allosterically controllable, metal-ion-triggered molecular switches. Specifically, we designed DNA sequences that adopt two low energy conformations, one of which does not bind to the target ion and the other of which contains mismatch sites serving as specific recognition elements for mercury(II) or silver(I) ions. Both switches contain multiple metal binding sites and thus exhibit homotropic allosteric (cooperative) responses. As heterotropic allosteric effectors we employ single-stranded DNA sequences that either stabilize or destabilize the nonbinding state, enabling dynamic range tuning over several orders of magnitude. The ability to rationally introduce these effects into target-responsive switches could be of value in improving the functionality of DNA-based nanomachines
Sequencing of folding events in Go-like proteins
We have studied folding mechanisms of three small globular proteins: crambin
(CRN), chymotrypsin inhibitor 2 (CI2) and the fyn Src Homology 3 domain (SH3)
which are modelled by a Go-like Hamiltonian with the Lennard-Jones
interactions. It is shown that folding is dominated by a well-defined
sequencing of events as determined by establishment of particular contacts. The
order of events depends primarily on the geometry of the native state.
Variations in temperature, coupling strengths and viscosity affect the
sequencing scenarios to a rather small extent. The sequencing is strongly
correlated with the distance of the contacting aminoacids along the sequence.
Thus -helices get established first. Crambin is found to behave like a
single-route folder, whereas in CI2 and SH3 the folding trajectories are more
diversified. The folding scenarios for CI2 and SH3 are consistent with
experimental studies of their transition states.Comment: REVTeX, 12 pages, 11 EPS figures, J. Chem. Phys (in press
High-precision gigahertz-to-terahertz spectroscopy of aqueous salt solutions as a probe of the femtosecond-to-picosecond dynamics of liquid water
Because it is sensitive to fluctuations occurring over femtoseconds to
picoseconds, gigahertz-to-terahertz dielectric relaxation spectroscopy can
provide a valuable window into water's most rapid intermolecular motions. In
response, we have built a vector network analyzer dielectric spectrometer
capable of measuring absorbance and index of refraction in this frequency
regime with unprecedented precision. Using this to determine the complex
dielectric response of water and aqueous salt solutions from 5.9 GHz to 1.12
THz (which we provide in the SI), we have obtained strong new constraints on
theories of water's collective dynamics. For example, while the
salt-dependencies we observe for water's two slower relaxations (8 and 1 ps)
are easily reconciled with suggestions that they arise due to rotations of
fully and partially hydrogen bonded molecules, respectively, the
salt-dependence of the fastest relaxation (180 fs) appears difficult to
reconcile with its prior assignment to liberations of single hydrogen bonds.Comment: 14 pages, 3 figures, Published in Journal of Chemical Physic
Origins of Chevron Rollovers in Non-Two-State Protein Folding Kinetics
Chevron rollovers of some proteins imply that their logarithmic folding rates
are nonlinear in native stability. This is predicted by lattice and continuum
G\=o models to arise from diminished accessibilities of the ground state from
transiently populated compact conformations under strongly native conditions.
Despite these models' native-centric interactions, the slowdown is due partly
to kinetic trapping caused by some of the folding intermediates' nonnative
topologies. Notably, simple two-state folding kinetics of small single-domain
proteins are not reproduced by common G\=o-like schemes.Comment: 10 pages, 4 Postscript figures (will appear on PRL
Thermodynamically Important Contacts in Folding of Model Proteins
We introduce a quantity, the entropic susceptibility, that measures the
thermodynamic importance-for the folding transition-of the contacts between
amino acids in model proteins. Using this quantity, we find that only one
equilibrium run of a computer simulation of a model protein is sufficient to
select a subset of contacts that give rise to the peak in the specific heat
observed at the folding transition. To illustrate the method, we identify
thermodynamically important contacts in a model 46-mer. We show that only about
50% of all contacts present in the protein native state are responsible for the
sharp peak in the specific heat at the folding transition temperature, while
the remaining 50% of contacts do not affect the specific heat.Comment: 5 pages, 5 figures; to be published in PR
Microsecond folding dynamics of the F13W G29A mutant of the B domain of staphylococcal protein A by laser-induced temperature jump
The small size (58 residues) and simple structure of the B domain of staphylococcal protein A (BdpA) have led to this domain being a paradigm for theoretical studies of folding. Experimental studies of the folding of BdpA have been limited by the rapidity of its folding kinetics. We report the folding kinetics of a fluorescent mutant of BdpA (G29A F13W), named F13W*, using nanosecond laser-induced temperature jump experiments. Automation of the apparatus has permitted large data sets to be acquired that provide excellent signal-to-noise ratio over a wide range of experimental conditions. By measuring the temperature and denaturant dependence of equilibrium and kinetic data for F13W*, we show that thermodynamic modeling of multidimensional equilibrium and kinetic surfaces is a robust method that allows reliable extrapolation of rate constants to regions of the folding landscape not directly accessible experimentally. The results reveal that F13W* is the fastest-folding protein of its size studied to date, with a maximum folding rate constant at 0 M guanidinium chloride and 45°C of 249,000 (s-1). Assuming the single-exponential kinetics represent barrier-limited folding, these data limit the value for the preexponential factor for folding of this protein to at least ≈2 x 10(6) s(-1)
Modeling study on the validity of a possibly simplified representation of proteins
The folding characteristics of sequences reduced with a possibly simplified
representation of five types of residues are shown to be similar to their
original ones with the natural set of residues (20 types or 20 letters). The
reduced sequences have a good foldability and fold to the same native structure
of their optimized original ones. A large ground state gap for the native
structure shows the thermodynamic stability of the reduced sequences. The
general validity of such a five-letter reduction is further studied via the
correlation between the reduced sequences and the original ones. As a
comparison, a reduction with two letters is found not to reproduce the native
structure of the original sequences due to its homopolymeric features.Comment: 6 pages with 4 figure
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