Ensemble properties of network rigidity reveal allosteric mechanisms.

The distance constraint model (DCM) is a unique computational modeling paradigm that integrates mechanical and thermodynamic descriptions of macromolecular structure. That is, network rigidity calculations are used to account for nonadditivity within entropy components, thus restoring the utility of free-energy decomposition. The DCM outputs a large number of structural characterizations that collectively allow for quantified stability-flexibility relationships (QSFR) to be identified.

Dynamics of coregulator-induced conformational perturbations in androgen receptor ligand binding domain.

Androgen receptor (AR) coregulators modulate ligand-induced gene expression in a tissue specific manner. The molecular events that follow coactivator binding to AR and the mechanisms that govern the sequence-specific effects of AR coregulators are poorly understood. Using consensus coactivator sequence D11-FxxLF and biophysical techniques, we show that coactivator association is followed by conformational rearrangement in AR ligand binding domain (AR-LBD) that is enthalpically and entropically favorable with activation energy of 29.

Understanding diversity of human innate immunity receptors: analysis of surface features of leucine-rich repeat domains in NLRs and TLRs.

Background: The human innate immune system uses a system of extracellular Toll-like receptors (TLRs) and intracellular Nod-like receptors (NLRs) to match the appropriate level of immune response to the level of threat from the current environment. Almost all NLRs and TLRs have a domain consisting of multiple leucine-rich repeats (LRRs), which is believed to be involved in ligand binding. LRRs, found also in thousands of other proteins, form a well-defined "horseshoe"-shaped structural scaffold that can be used for a variety of functions, from binding specific ligands to performing a general structural role.

Kinetic and thermodynamic characterization of dihydrotestosterone-induced conformational perturbations in androgen receptor ligand-binding domain.

Ligand-induced conformational perturbations in androgen receptor (AR) are important in coactivator recruitment and transactivation. However, molecular rearrangements in AR ligand-binding domain (AR-LBD) associated with agonist binding and their kinetic and thermodynamic parameters are poorly understood. We used steady-state second-derivative absorption and emission spectroscopy, pressure and temperature perturbations, and 4,4'-bis-anilinonaphthalene 8-sulfonate (bis-ANS) partitioning to determine the kinetics and thermodynamics of the conformational changes in AR-LBD after dihydrotestosterone (DHT) binding.

On the role of structural class of a protein with two-state folding kinetics in determining correlations between its size, topology, and folding rate.

The time it takes for proteins to fold into their native states varies over several orders of magnitude depending on their native-state topology, size, and amino acid composition. In a number of previous studies, it was found that there is strong correlation between logarithmic folding rates and contact order for proteins that fold with two-state kinetics, while such correlation is absent for three-state proteins. Conversely, strong correlations between folding rates and chain length occur within three-state proteins, but not in two-state proteins.

New insight into long-range nonadditivity within protein double-mutant cycles.

Additivity principles in chemistry, biochemistry, and biophysics have been used extensively for decades. Nevertheless, it is well known that additivity frequently breaks down in complex biomacromolecules. Nonadditivity within protein double mutant free energy cycles of spatially close residue pairs is a generally well-understood phenomenon, whereas a robust description of nonadditivity extending over large distances remains to be developed.

Elliptic and circular dichroism effects in two-photon double ionization of atoms.

An ab initio parametrization of the two-photon double ionization amplitude from an s2 subshell of an atom in a 1S state is presented and used to predict two light polarization effects on photoelectron angular distributions that do not exist in single-photon double ionization: (i) elliptic dichroism and (ii) circular dichroism at equal energy sharing. Estimates for He show large magnitudes for these effects, which provide a means for polarization control of double ionization by vacuum ultraviolet light.

Nondipole effects in photo-double-ionization of He by a vuv photon.

We present a dynamical model-independent, ab initio parametrization of the quadrupole transition amplitude for photo-double-ionization of He. An asymmetry of the triple differential cross section induced by the nondipole corrections is discussed and shown to be significant even for an excess energy as low as 80 eV. We provide predictions for two different kinds of experiments in which nondipole effects should be observable with current experimental capabilities.