The growing interest in the complexity of biological interactions is continuously driving the need to increase system size in biophysical simulations, requiring not only powerful and advanced hardware but adaptable software that can accommodate a large number of atoms interacting through complex forcefields. To address this, we developed and implemented strategies in the GENESIS molecular dynamics package designed for large numbers of processors. Long-range electrostatic interactions were parallelized by minimizing the number of processes involved in communication. A novel algorithm was implemented for nonbonded interactions to increase single instruction multiple data (SIMD) performance, reducing memory usage for ultra large systems.Memory usage for neighbor searches in real-space nonbonded interactions was reduced by approximately 80%, leading to significant speedup. Using experimental data describing physical 3D chromatin interactions, we constructed the first atomistic model of an entire gene locus (GATA4). Taken together, these developments enabled the first billion-atom simulation of an intact biomolecular complex, achieving scaling to 65,000 processes (130,000 processor cores) with

We approach the problem of coil−globule transition dynamics numerically by Brownian dynamics simulations. This method allows us to study the behavior of polymer chains of varying stiffness and the effects of bending stiffness on chain morphology during the process of coil− globule collapse, imitating globule formation in poor solvent conditions. We record and analyze a three-stage process of globule formation for flexible chains: (1) nucleation, (2) coalescence of nuclei, and (3) collapsed globule formation. Stiffer chains undergo similar formation stages; however, the "raindrops" formed by these chains are elongated (unlike spherical structures formed by flexible chains) and exhibit regular packing of chains into antiparallel hairpin structures. In order to assess the transition dynamics quantitatively, polymer chain configurations were analyzed by generating contact maps and contact frequency histograms for all given configurations. These clusters are initial-configuration-dependent, and their growth and intercluster contacts have direct analogy with the process of raindrop coalescence.

We study the dynamics of polymer chain collapse into a globular state in poor solvent, as a function of chain flexibility. We examine the compactness of the folded globule assessing the direct contact and a larger length-scale structural characteristics at various persistence lengths l p. We discover that semiflexible polymer chains with a specific stiffness (l p ≈ 8 monomers) form the most densely folded structures, independently of the chain length, a phenomenon due to nematic-like hairpin formation and stacking of hairpin segments in the most compact state. Even in this most compactly folded state, the number of contacts between monomers (accounting for covalent bonds as well as noncovalent physical interactions) is still low, and the globule is only just above the marginal stability threshold. We identify morphological changes associated with the dynamics of semiflexible chain collapse: flexible chains fold into globules, less flexible form rod-like structures, followed by toroidal structures of different geni, and finally, even stiffer chains form highly elongated rods. We also study the time of collapse as a function of persistence length, which shows that stiff chains take much longer to reach their elongated lowest energy state. We propose that polymer chain stiffness, as a regulator of both local and global chain compactness, is highly important in biological systems and in the dynamics of DNA and protein folding.

We re-examine the physical origin of the polymer glass transition from the point of view of marginal rigidity, which is achieved at a certain average number of mechanically active intermolecular contacts per monomer. In the case of polymer chains in a melt/poor solvent, each monomer has two neighbors bound by covalent bonds and also a number of central-force contacts modelled by the Lennard-Jones (LJ) potential. We find that when the average number of contacts per monomer (covalent and non-covalent) exceeds the critical value z* ≈ 4, the system becomes solid and the dynamics arrested - a state that we declare the glass. Coarse-grained Brownian dynamics simulations show that at sufficient strength of LJ attraction (which effectively represents the depth of quenching, or the quality of solvent) the polymer globule indeed crosses the threshold of z*, and becomes a glass with a finite zero-frequency shear modulus, G∝ (z-z*). We verify this by showing the distinction between the 'liquid' polymer droplet at z < z*, which changes shape and adopts the spherical conformation in equilibrium, and the glassy 'solid' droplet at z > z*, which retains its shape frozen at the moment of z* crossover. These results provide a robust microscopic criterion to tell the liquid apart from the glass for the linear polymers.

The problem of transport through nanochannels is one of the major questions in cell biology, with a wide range of applications. In this paper we discuss the process of spontaneous translocation of molecules (Brownian particles) by ratcheted diffusion: a problem relevant for protein translocation along bacterial flagella or injectosome complex, or DNA translocation by bacteriophages. We use molecular dynamics simulations and statistical theory to identify two regimes of transport: at low rate of particle injection into the channel the process is controlled by the individual diffusion towards the open end (the first passage problem), while at a higher rate of injection the crowded regime sets in. In this regime the particle density in the channel reaches a constant saturation level and the resistance force increases substantially, due to the osmotic pressure build-up. To achieve a steady-state transport, the apparatus that injects new particles into a crowded channel has to operate with an increasing power consumption, proportional to the length of the channel and the required rate of transport. The analysis of resistance force, and accordingly -the power required to inject the particles into a crowded channel to overcome its clogging, is also relevant for many microfluidics applications.