Magdalena Gruziel

Chirality inversions in self-assembly of fibrillar superstructures: a computational study

The formation of aggregates of helical fibrils is analyzed numerically. The aggregate morphology, chirality and stability are studied as a function of temperature and helical pitch of individual fibrils. The simulations show the existence of a critical pitch above which the handedness of the aggregates is opposite to that of the constituting fibrils. We also observe and analyze the process of spontaneous chirality inversion of individual fibrils within the aggregates. This inversion is accompanied by a helical wave propagating along the fibril axis, with a kink separating left-handed and right-handed regions moving along the fibril. The frequency of this process is strongly dependent on the initial pitch of the fibrils with a local maximum near the critical pitch.

The Poisson-Boltzmann model for tRNA: Assessment of the calculation set-up and ionic concentration cutoff

Using tRNA molecule as an example, we evaluate the applicability of the Poisson‐Boltzmann model to highly charged systems such as nucleic acids. Particularly, we describe the effect of explicit crystallographic divalent ions and water molecules, ionic strength of the solvent, and the linear approximation to the Poisson‐Boltzmann equation on the electrostatic potential and electrostatic free energy. We calculate and compare typical similarity indices and measures, such as Hodgkin index and root mean square deviation. Finally, we introduce a modification to the nonlinear Poisson‐Boltzmann equation, which accounts in a simple way for the finite size of mobile ions, by applying a cutoff in the concentration formula for ionic distribution at regions of high electrostatic potentials. We test the influence of this ionic concentration cutoff on the electrostatic properties of tRNA.

Hydration free energy of a Model Lennard-Jones solute particle: Microscopic Monte Carlo simulation studies, and interpretation based on mesoscopic models

In this study, the hydration of a model Lennard-Jones solute particle and the analytical approximations of the free energy of hydration as functions of solute microscopic parameters are analyzed. The control parameters of the solute particle are the charge, the Lennard-Jones diameter, and also the potential well depth. The obtained multivariate free energy functions of hydration were parametrized based on Metropolis Monte Carlo simulations in the extended NpT ensemble, and interpreted based on mesoscopic solvation models proposed by Gallicchio and Levy [J. Comput. Chem. 25, 479 (2004)], and Wagoner and Baker [Proc. Natl. Acad. Sci. U.S.A. 103, 8331 (2006)]. Regarding the charge and the solute diameter, the dependence of the free energy on these parameters is in qualitative agreement with former studies. The role of the third parameter, the potential well depth not previously considered, appeared to be significant for sufficiently precise bivariate solvation free energy fits. The free energy fits for cations and neutral solute particles were merged, resulting in a compact manifold of the free energy of solvation. The free energy of hydration for anions forms two separate manifolds, which most likely results from an abrupt change of the coordination number when changing the size of the anion particle.

SELECTED MICROSCOPIC AND MEZOSCOPIC MODELLING TOOLS AND MODELS - AN OVERVIEW

In order to model (bio)molecular systems and to simulate their dynamics one requires the potential energy functions at the microscopic, classical and/or quantum levels, as well as fast generators of the free-energy functions at the mezoscopic level. A brief overview of the methods which allow computations of the potential energy functions and the free energies is presented. The ongoing research is focused on designing molecular mezoscopic interaction potentials, applicable to nanoscale (bio)molecular systems, and on utilizing conformationally dependent atomic charges. In particular, the coupling of a fast quantum SCC-DFTB method with the Poisson-Boltzmann (PB) or Generalized Born (GB) models is discussed, and the role of the SCC-DFTB CM3 charges in computations of the mean-field electrostatic energies of molecular systems in real molecular environments is indicated. These charges reproduce very well molecular dipole moments, and are obtained from the Mulliken ones by applying a mapping procedure, using a quadratic function of the Mayer’s bond orders. The PB and GB models give electrostatic reaction field energies of molecular environments, in particular, provide electrostatic contributions to the salvation energies. It is assumed that the solvation energy consists of the mean-field electrostatic and nonpolar (hydrophobic) energy contributions. Typically, the nonpolar term consists of the cavity formation free energy, and sometimes also of a mean van der Waals interaction energy of the molecular system with its environment. This allows to reproduce experimental solvation/hydration energies assuming different analytical forms of the nonpolar energy terms. Refined GB models, with new formulae for the Born radii are discussed. The nonpolar energies are quite well reproduced using the solvent accessible surface area (SASA), or a polynomial series depending on reciprocal values of the Born radii. Presence of the mean van der Waals energy on the quality of the fits is also discussed. Reliable mezoscopic models and theories play a key role in describing the functioning of nanoscale (bio)molecular systems