Two center multipole expansion method: application to macromolecular systems

We propose a new theoretical method for the calculation of the interaction energy between macromolecular systems at large distances. The method provides a linear scaling of the computing time with the system size and is considered as an alternative to the well known fast multipole method. Its efficiency, accuracy and applicability to macromolecular systems is analyzed and discussed in detail.Comment: 23 pages, 7 figures, 1 tabl

Macromolecular crowding modulates folding mechanism of alpha/beta protein apoflavodoxin

Protein dynamics in cells may be different from that in dilute solutions in vitro since the environment in cells is highly concentrated with other macromolecules. This volume exclusion due to macromolecular crowding is predicted to affect both equilibrium and kinetic processes involving protein conformational changes. To quantify macromolecular crowding effects on protein folding mechanisms, here we have investigated the folding energy landscape of an alpha/beta protein, apoflavodoxin, in the presence of inert macromolecular crowding agents using in silico and in vitro approaches. By coarse-grained molecular simulations and topology-based potential interactions, we probed the effects of increased volume fraction of crowding agents (phi_c) as well as of crowding agent geometry (sphere or spherocylinder) at high phi_c. Parallel kinetic folding experiments with purified Desulfovibro desulfuricans apoflavodoxin in vitro were performed in the presence of Ficoll (sphere) and Dextran (spherocylinder) synthetic crowding agents. In conclusion, we have identified in silico crowding conditions that best enhance protein stability and discovered that upon manipulation of the crowding conditions, folding routes experiencing topological frustrations can be either enhanced or relieved. The test-tube experiments confirmed that apoflavodoxin's time-resolved folding path is modulated by crowding agent geometry. We propose that macromolecular crowding effects may be a tool for manipulation of protein folding and function in living cells.Comment: to appear in Biophysical Journal (2009). to appear in Biophysical Journal (2009

Molecular Dynamics Simulation of Macromolecules Using Graphics Processing Unit

Molecular dynamics (MD) simulation is a powerful computational tool to study the behavior of macromolecular systems. But many simulations of this field are limited in spatial or temporal scale by the available computational resource. In recent years, graphics processing unit (GPU) provides unprecedented computational power for scientific applications. Many MD algorithms suit with the multithread nature of GPU. In this paper, MD algorithms for macromolecular systems that run entirely on GPU are presented. Compared to the MD simulation with free software GROMACS on a single CPU core, our codes achieve about 10 times speed-up on a single GPU. For validation, we have performed MD simulations of polymer crystallization on GPU, and the results observed perfectly agree with computations on CPU. Therefore, our single GPU codes have already provided an inexpensive alternative for macromolecular simulations on traditional CPU clusters and they can also be used as a basis to develop parallel GPU programs to further speedup the computations.Comment: 21 pages, 16 figure

A new approach to high resolution, high contrast electron microscopy of macromolecular block copolymer assemblies

Determining the structure of macromolecular samples is vital for understanding and adapting their function. Transmission electron microscopy (TEM) is widely used to achieve this, but, owing to the weak electron scattering cross-section of carbon, TEM images of macromolecular samples are generally low contrast and low resolution. Here we implement a fast and practically simple routine to achieve high-contrast imaging of macromolecular samples using exit wave reconstruction (EWR), revealing a new level of structural detail. This is only possible using ultra-low contrast supports such as the graphene oxide (GO) used here and as such represents a novel application of these substrates. We apply EWR on GO membranes to study self-assembled block copolymer structures, distinguishing not only the general morphology or nanostructure, but also evidence for the substructure (i.e. the polymer chains) which gives insight into their formation mechanisms and functional properties

Stochastic dynamics of macromolecular-assembly networks

The formation and regulation of macromolecular complexes provides the backbone of most cellular processes, including gene regulation and signal transduction. The inherent complexity of assembling macromolecular structures makes current computational methods strongly limited for understanding how the physical interactions between cellular components give rise to systemic properties of cells. Here we present a stochastic approach to study the dynamics of networks formed by macromolecular complexes in terms of the molecular interactions of their components. Exploiting key thermodynamic concepts, this approach makes it possible to both estimate reaction rates and incorporate the resulting assembly dynamics into the stochastic kinetics of cellular networks. As prototype systems, we consider the lac operon and phage lambda induction switches, which rely on the formation of DNA loops by proteins and on the integration of these protein-DNA complexes into intracellular networks. This cross-scale approach offers an effective starting point to move forward from network diagrams, such as those of protein-protein and DNA-protein interaction networks, to the actual dynamics of cellular processes.Comment: Open Access article available at http://www.nature.com/msb/journal/v2/n1/full/msb4100061.htm