Section: New Results

Modeling the flexibility of macro-molecules

Keywords: protein, flexibility, collective coordinate, conformational sampling dimensionality reduction.

Wang-Landau Algorithm: an adapted random walk to boost convergence

Participants : F. Cazals, A. Chevallier.

The Wang-Landau (WL) algorithm is a recently developed stochastic algorithm computing densities of states of a physical system, and also performing numerical integration in high dimensional spaces. Since its inception, it has been used on a variety of (bio-)physical systems, and in selected cases, its convergence has been proved. The convergence speed of the algorithm is tightly tied to the connectivity properties of the underlying random walk.

In this work [19], we propose an efficient random walk that uses geometrical information to circumvent the following inherent difficulties: avoiding overstepping strata, toning down concentration phenomena in high-dimensional spaces, and accommodating multidimensional distributions. These improvements are especially well suited to improve calculations on a per basin basis – included anharmonic ones.

Experiments on various models stress the importance of these improvements to make WL effective in challenging cases. Altogether, these improvements make it possible to compute density of states for regions of the phase space of small biomolecules.

Survey of the analysis of continuous conformational variability of biological macromolecules by electron microscopy

Participant : F. Cazals.

In collaboration with a group of colleagues led by J. M. Carazo, CSIC, Biocomputing Unit, National Center for Biotechnology, Spain.

Single-particle analysis by electron microscopy is a well established technique for analyzing the three-dimensional structures of biological macromolecules. Besides its ability to produce high-resolution structures, it also provides insights into the dynamic behavior of the structures by elucidating their conformational variability. In this work [17], the different image-processing methods currently available to study continuous conformational changes are reviewed.