Polymer-theory insights into biomolecular systems

Boosted by the technological advances in experimental techniques, cellular biology is nowadays facing the need for quantitative approaches in order to rationalize the huge amount of collected data. A particularly succesfull theoretical framework is provided by Polymer Theory which, combined with molecular simulations, can capture the essential features of biomacromolecules and describe the cellular processes they participate to. This thesis provides a compendium of works showing the strength of this combination. In a first project, we model the twisting properties of amyloid fibrils by means of a simple coarse-grained approach, based on the competition between elasticity and electrostatic repulsion of nearby portions of the fibrils. The model quantitatively recapitulates the evolution of fibril periodicity as a function of the ionic strength of the solution and of the fibril width. A universal mesoscopic structural signature of the fibrils emerges from this picture, predicting a general, parameter-free law for the periodicity of the fibrils which is validated on several experimental results. A second work is focused on the role played by mitochondrial Hsp70 chaperone in the import of cytoplasmic proteins. Particularly, we computed by means of molecular simulations the effective free-energy profile for substrate translocation upon chaperone binding. We then used the resulting free energy to quantitatively characterize the kinetics of the import process and outline the essential role played by Hsp70 in this context. Finally, in a third project we studied the shape properties of a polymer under tension, a physical condition typically realized both in single-molecule experiments and in vivo. By means of analytical calculations and Monte Carlo simulations, we develop a theoretical framework which quantitatively describes these properties, highlighting the interplay between external force and chain size in determining the spatial distribution of a stretched chain.

Experimental Method to Distinguish between a Solution and a Suspension

Paulo Henrique Jacob Silva, Ting Mao, Quy Ong Khac, Francesco Stellacci, Xufeng Xu

Dispersion of objects in a fluid phase can be classified as solutions (Gibbs free energy of mixing, Delta G(mix) < 0) or suspensions (Delta G(mix) > 0) depending on their thermodynamic stability. Small objects tend to form solutions, larger ones suspensions, e.g., molecules versus micrometer-sized colloids. Proteins and nanomaterials fall between these two size regimes. The long-standing issue of whether proteins and nanoparticles are dissolved or suspended remains an important research question. Here, a simple, versatile, and experimentally robust method, based on sedimentation equilibrium analytical ultracentrifugation (SE-AUC), which can determine whether proteins, nanoparticles, or polymers form solutions or suspensions, is presented. SE-AUC determines the osmotic pressure profile for a dispersion. Such a profile for solutions (equilibrium one-phase systems) is independent of the initial and the operating conditions. The opposite is true for suspensions that are nonequilibrium two-phase systems. This study proves that bovine serum albumin and lysozyme form solutions while ferritin and apoferritin form suspensions.

WILEY2022

The Shape of a Stretched Polymer

Salvatore Assenza, Paolo De Los Rios, Alberto Stefano Sassi

The shape of a polymer plays an important role in determining its interactions with other molecules and with the environment, and is in turn affected by both of them. As a consequence, in the literature the shape properties of a chain in many different conditions have been investigated. Here, we characterize the shape and orientational properties of a polymer chain under tension, a physical condition typically realized both in single-molecule experiments and in vivo. By means of analytical calculations and Monte Carlo simulations, we develop a theoretical framework which quantitatively describes these properties, highlighting the interplay between external force and chain size in determining the spatial distribution of a stretched chain.

2017

Ab Initio Flexible Force Field for Metal-Organic Frameworks Using Dummy Model Coordination Bonds

Sudabeh Jawahery, Seyedmohamad Moosavi, Nakul Rampal, Berend Smit, Matthew David Witman

We present force fields developed from periodic density functional theory (DFT) calculations that can be used in classical molecular simulations to model M MOF-74 (M = Co, Fe, Mg, Mn, Ni, Zn) and its extended linker analogs. Our force fields are based on cationic dummy models (CDMs). These dummy models simplify the methodology required to tune the parameters and improve the accuracy of the force fields. We used our force fields to compare mechanical properties across the M MOF-74 series and determine that increasing the size of the linker decreases the framework rigidity. In addition, we applied our force fields to an extended linker analog of Mg-MOF-74 and characterized the free energy of a previously reported deformation pattern in which the one-dimensional hexagonal channels of the framework become irregular. The free energy profiles confirm that the deformation is adsorbate induced and impossible to access solely by a pressure stimulus. On the basis of our results, we conclude that the force fields presented here and others that may be developed using our methodology are transferable across metal organic framework series that share a metal center topology. Finally, we believe that these force fields have the potential to be adapted for the study of complex problems in MOF chemistry, including defects and crystal growth, that have thus far been beyond the scope of classical molecular simulations.

2019