Over the past 10 years, several scientific thrusts have come together in the study of flavanoids that make it possible to move forward into the study of complexation between polyphenols and polypeptides. Enhanced understanding of the conformational properties of flavanoid monomers and polyflavanoids through molecular modeling, combined with the detailed NMR experimental data now in’ the literat...

Computational prediction of structure for macromolecular fragments is a formidable challenge. Here we show that the differences in conformational thermodynamics, computed using the equilibrium distribution of dihedral angles from molecular dynamics simulation, can identify the better model for the missing residues in the metal ion free (apo) skeletal muscle Troponin C (TnC). We use the model to...

Structural changes are critical for biological functions of proteins and describing conformational changes in large macromolecular complexes is a major challenge. To allow full studies of gradual conformational changes, we have recently developed Hybrid Electron Microscopy Normal Mode Analysis (HEMNMA) [1]. HEMNMA uses normal modes to elastically align electron microscopy (EM) images with a ref...

A multivariate analysis of the backbone and sugar torsion angles of dinucleotide fragments was used to construct a 3D principal conformational subspace (PCS) of DNA duplex crystal structures. The potential energy surface (PES) within the PCS was mapped for a single-strand dinucleotide model using an empirical energy function. The low energy regions of the surface encompass known DNA forms and a...

A hybrid Monte Carlo method with adaptive temperature choice is presented, which exactly generates the distribution of a mixed-canonical ensemble composed of two canonical ensembles at low and high temperature. The analysis of resulting Markov chains with the reweighting technique shows an efficient sampling of the canonical distribution at low temperature, whereas the high temperature componen...

Estimation of configurational entropy from molecular dynamics trajectories is a difficult task which is often performed using quasi-harmonic or histogram analysis. An entirely different approach, proposed recently, estimates local density distribution around each conformational sample by measuring the distance from its nearest neighbors. In this work we show this theoretically well grounded the...

Motivation. To assist efforts in determining and exploring the functional properties of proteins, it is desirable to characterize and predict protein flexibilities. Results. In this study, the conformational entropy is used as an indicator of the protein flexibility. We first explore whether the conformational change can capture the protein flexibility. The well-defined decoy structures are con...

Human α-Synuclein (αSyn) is a natively unfolded protein whose aggregation into amyloid fibrils is involved in Parkinson disease. A full comprehension of the structure and dynamics of early intermediates leading to the aggregated states is an unsolved problem of essential importance in deciphering the molecular mechanisms of αSyn aggregation and formation of fibrils. Traditional bulk techniques ...

It was shown decades ago that purified 30S ribosome subunits readily interconvert between "active" and "inactive" conformations in a switch that involves changes in the functionally important neck and decoding regions. However, the physiological significance of this conformational change had remained unknown. In exponentially growing Escherichia coli cells, RNA SHAPE probing revealed that 16S r...

Many fundamental cellular processes such as gene expression are tightly regulated by protein allostery. Allosteric signal propagation from the regulatory to the active site requires long-range communication, the molecular mechanism of which remains a matter of debate. A classical example for long-range allostery is the activation of the methionine repressor MetJ, a transcription factor. Binding...