arXiv subjects

Lorant Janosi

Publications and source records attributed to Lorant Janosi.

5 recordsLinked to original sources

arXiv2011

Kinetic Monte Carlo and Cellular Particle Dynamics Simulations of Multicellular Systems

Computer modeling of multicellular systems has been a valuable tool for interpreting and guiding in vitro experiments relevant to embryonic morphogenesis, tumor growth, angiogenesis and, lately, structure formation following the printing of cell aggregates as bioink particles. Computer simulations based on Metropolis Monte Carlo (MMC) algorithms were successful in explaining and predicting the resulting stationary structures (corresponding to the lowest adhesion energy state). Here we present two alternatives to the MMC approach for modeling cellular motion and self-assembly: (1) a kinetic Monte Carlo (KMC), and (2) a cellular particle dynamics (CPD) method. Unlike MMC, both KMC and CPD methods are capable of simulating the dynamics of the cellular system in real time. In the KMC approach a transition rate is associated with possible rearrangements of the cellular system, and the corresponding time evolution is expressed in terms of these rates. In the CPD approach cells are modeled as interacting cellular particles (CPs) and the time evolution of the multicellular system is determined by integrating the equations of motion of all CPs. The KMC and CPD methods are tested and compared by simulating two experimentally well known phenomena: (1) cell-sorting within an aggregate formed by two types of cells with different adhesivities, and (2) fusion of two spherical aggregates of living cells.

physics.bio-ph↗

arXiv2008

Calculating free energy profiles in biomolecular systems from fast non-equilibrium processes

Often gaining insight into the functioning of biomolecular systems requires to follow their dynamics along a microscopic reaction coordinate (RC) on a macroscopic time scale, which is beyond the reach of current all atom molecular dynamics (MD) simulations. A practical approach to this inherently multiscale problem is to model the system as a fictitious overdamped Brownian particle that diffuses along the RC in the presence of an effective potential of mean force (PMF) due to the rest of the system. By employing the recently proposed FR method [I. Kosztin et al., J. of Chem. Phys. 124, 064106 (2006)], which requires only a small number of fast nonequilibrium MD simulations of the system in both forward and time reversed directions along the RC, we reconstruct the PMF: (1) of deca-alanine as a function of its end-to-end distance, and (2) that guides the motion of potassium ions through the gramicidin A channel. In both cases the computed PMFs are found to be in good agreement with previous results obtained by different methods. Our approach appears to be about one order of magnitude faster than the other PMF calculation methods and, in addition, it also provides the position dependent diffusion coefficient along the RC. Thus, the obtained PMF and diffusion coefficient can be used in a suitable stochastic model to estimate important characteristics of the studied systems, e.g., the mean folding time of the stretched deca-alanine and the mean diffusion time of the potassium ion through gramicidin A.

physics.bio-ph↗

arXiv2006

Theoretical prediction of spectral and optical properties of bacteriochlorophylls in thermally disordered LH2 antenna complexes

A general approach for calculating spectral and optical properties of pigment-protein complexes of known atomic structure is presented. The method, that combines molecular dynamics simulations, quantum chemistry calculations and statistical mechanical modeling, is demonstrated by calculating the absorption and circular dichroism spectra of the B800-B850 BChls of the LH2 antenna complex from Rs. molischianum at room temperature. The calculated spectra are found to be in good agreement with the available experimental results. The calculations reveal that the broadening of the B800 band is mainly caused by the interactions with the polar protein environment, while the broadening of the B850 band is due to the excitonic interactions. Since it contains no fitting parameters, in principle, the proposed method can be used to predict optical spectra of arbitrary pigment-protein complexes of known structure.

physics.bio-ph↗

arXiv2005

Calculating potentials of mean force and diffusion coefficients from nonequilibirum processes without Jarzynski's equality

In general, the direct application of the Jarzynski equality (JE) to reconstruct potentials of mean force (PMFs) from a small number of nonequilibrium unidirectional steered molecular dynamics (SMD) paths is hindered by the lack of sampling of extremely rare paths with negative dissipative work. Such trajectories, that transiently violate the second law, are crucial for the validity of JE. As a solution to this daunting problem, we propose a simple and efficient method, referred to as the FR method, for calculating simultaneously both the PMF U(z) and the corresponding diffusion coefficient D(z) along a reaction coordinate z for a classical many particle system by employing a small number of fast SMD pullings in both forward (F) and time reverse (R) directions, without invoking JE. By employing Crook's transient fluctuation theorem (that is more general than JE) and the stiff spring approximation, we show that: (i) the mean dissipative work W_d in the F and R pullings are equal, (ii) both U(z) and W_d can be expressed in terms of the easily calculable mean work of the F and R processes, and (iii) D(z) can be expressed in terms of the slope of W_d. To test its viability, the FR method is applied to determine U(z) and D(z) of single-file water molecules in single-walled carbon nanotubes (SWNTs). The obtained U(z) is found to be in very good agreement with the results from other PMF calculation methods, e.g., umbrella sampling. Finally, U(z) and D(z) are used as input in a stochastic model, based on the Fokker-Planck equation, for describing water transport through SWNTs on a mesoscopic time scale that in general is inaccessible to MD simulations.

cond-mat.stat-mech↗

arXiv2005

Influence of subunit structure on the oligomerization state of light harvesting complexes: a free energy calculation study

Light harvesting complexes 2 (LH2) from Rhodospirillum (Rs.) molischianum and Rhodopseudomonas (Rps.) acidophila form ring complexes out of eight or nine identical subunits, respectively. Here, we investigate computationally what factors govern the different ring sizes. Starting from the crystal structure geometries, we embed two subunits of each species into their native lipid-bilayer/water environment. Using molecular dynamics simulations with umbrella sampling and steered molecular dynamics, we probe the free energy profiles along two reaction coordinates, the angle and the distance between two subunits. We find that two subunits prefer to arrange at distinctly different angles, depending on the species, at about 42.5 deg for Rs. molischianum and at about 38.5 deg for Rps. acidophila, which is likely to be an important factor contributing to the assembly into different ring sizes. Our calculations suggest a key role of surface contacts within the transmembrane domain in constraining these angles, whereas the strongest interactions stabilizing the subunit dimers are found in the C-, and to a lesser extent, N-terminal domains. The presented computational approach provides a promising starting point to investigate the factors contributing to the assembly of protein complexes, in particular if combined with modeling of genetic variants.

physics.bio-ph↗