Fabio Trovato

Pennsylvania State University, Chemistry, Post-Doc

Followers

Following

Co-authors

Public Views

To be updated

less

James Elkins

School of the Art Institute of Chicago

Eddie Ti Tjih TAN

Universiti Teknologi Mara

Hanaa Ahmed

Animal Health Research Institute

Irina Kolesnik

Moscow State University

Prof. Tofazzal Islam

Bangabandhu Sheikh Mujibur Rahman Agricultural University

Kiran Dasari

University of Illinois at Urbana-Champaign

Hernan Chaimovich

Universidade de São Paulo

Professor Dr. Loutfy H . Madkour

Al-Baha University, Kingdom of Saudi Arabia

amin mridha

King Saud University

Benoit Roux

University of Chicago

Interests

Uploads

Papers by Fabio Trovato

Cotranslational Protein Folding inside the Ribosome Exit Tunnel

Cell Reports, 2015

At what point during translation do proteins fold? It is well established that proteins can fold ... more At what point during translation do proteins fold? It is well established that proteins can fold cotranslationally outside the ribosome exit tunnel, whereas studies of folding inside the exit tunnel have so far detected only the formation of helical secondary structure and collapsed or partially structured folding intermediates. Here, using a combination of cotranslational nascent chain force measurements, inter-subunit fluorescence resonance energy transfer studies on single translating ribosomes, molecular dynamics simulations, and cryoelectron microscopy, we show that a small zinc-finger domain protein can fold deep inside the vestibule of the ribosome exit tunnel. Thus, for small protein domains, the ribosome itself can provide the kind of sheltered folding environment that chaperones provide for larger proteins.

RNA dynamics with one-bead coarse-grained model

by Valentina Tozzini, Joanna Trylska, and Fabio Trovato

Application of an evolutionary algorithm to the coarse-grained force field optimization problem

by Valentina Tozzini, Joanna Trylska, and Fabio Trovato

Diffusion within the Cytoplasm: A Mesoscale Model of Interacting Macromolecules

by Fabio Trovato and Valentina Tozzini

Biophysical Journal, 2014

Recent experiments carried out in the dense cytoplasm of living cells have highlighted the import... more Recent experiments carried out in the dense cytoplasm of living cells have highlighted the importance of proteome composition and nonspecific intermolecular interactions in regulating macromolecule diffusion and organization. Despite this, the dependence of diffusion-interaction on physicochemical properties such as the degree of poly-dispersity and the balance between steric repulsion and nonspecific attraction among macromolecules was not systematically addressed. In this work, we study the problem of diffusion-interaction in the bacterial cytoplasm, combining theory and experimental data to build a minimal coarse-grained representation of the cytoplasm, which also includes, for the first time to our knowledge, the nucleoid. With stochastic molecular-dynamics simulations of a virtual cytoplasm we are able to track the single biomolecule motion, sizing from 3 to 80 nm, on submillisecond-long trajectories. We demonstrate that the size dependence of diffusion coefficients, anomalous exponents, and the effective viscosity experienced by biomolecules in the cytoplasm is fine-tuned by the intermolecular interactions. Accounting only for excluded volume in these potentials gives a weaker size-dependence than that expected from experimental data. On the contrary, adding nonspecific attraction in the range of 1-10 thermal energy units produces a stronger variation of the transport properties at growing biopolymer sizes. Normal and anomalous diffusive regimes emerge straightforwardly from the combination of high macromolecular concentration, poly-dispersity, stochasticity, and weak nonspecific interactions. As a result, small biopolymers experience a viscous cytoplasm, while the motion of big ones is jammed because the entanglements produced by the network of interactions and the entropic effects caused by poly-dispersity are stronger.

Download

Minimalist models for biopolymers: Open problems, latest advances and perspectives

by Valentina Tozzini and Fabio Trovato

A Minimalist Model of Protein Diffusion and Interactions: The Green Fluorescent Protein within the Cytoplasm

by Valentina Tozzini and Fabio Trovato

Macromolecules, 2013

ABSTRACT In this work, we present a minimalist model (one-bead-per-amino acid resolution) of a tr... more ABSTRACT In this work, we present a minimalist model (one-bead-per-amino acid resolution) of a tracer protein (the green fluorescent protein) embedded in a meso scale cytoplasm (one-bead-per-crowder) for molecular dynamics simulations. The extremely low computational cost of the model allows a statistically relevant exploration of the tracer diffusive dynamics. The accurate description of diffusion and interactions is maintained by means of a careful choice of the functional forms and parameters of the force field terms, optimized by means of a semiheuristic strategy involving the use of a genetic algorithm. Consequently, the model is capable of implicitly reincluding some effects lost in the coarse graining, such as the shape effects (for crowders), hydrodynamics and correlations, hydration/dehydration and interaction specificity (for the tracer). The result is an accurate representation of the multiscale dynamics of the tracer, involving its internal flexibility, specific protein−protein interactions and diffusion. http://pubs.acs.org/articlesonrequest/AOR-Nxsg4MfMWvH3IfNeQ2zA

Evolutionary Algorithm in the Optimization of a Coarse-Grained Force Field

by Valentina Tozzini, Joanna Trylska, and Fabio Trovato

Journal of Chemical Theory and Computation, 2013

ABSTRACT Simulations using residue-scale coarse-grained models of biomolecules are less computati... more ABSTRACT Simulations using residue-scale coarse-grained models of biomolecules are less computationally demanding than simulations employing full-atomistic force fields. However, the coarse-grained models are often difficult and tedious to parametrize for certain applications. Therefore, a systematic and objective method to help develop or adapt the coarse-grained models is needed. We present an automatic method that implements an evolutionary algorithm to find a set of optimal force field parameters for a one-bead coarse-grained model. In addition to an optimized force field, parameter correlations and significance of the potential energy terms can be determined. The method is applied to two classes of problems: the dynamics of an RNA helix and the RNA structure prediction.

Homeotic proteins participate in the function of human-DNA replication origins

by Stefano Luin, Fabio Trovato, and G. Abdurashidova

Nucleic Acids Research, 2010

Recent evidence points to homeotic proteins as actors in the crosstalk between development and DN... more Recent evidence points to homeotic proteins as actors in the crosstalk between development and DNA replication. The present work demonstrates that HOXC13, previously identified as a new member of human DNA replicative complexes, is a stable component of early replicating chromatin in living cells: it displays a slow nuclear dynamics due to its anchoring to the DNA minor groove via the arginine-5 residue of the homeodomain. HOXC13 binds in vivo to the lamin B2 origin in a cell-cycle-dependent manner consistent with origin function; the interaction maps with nucleotide precision within the replicative complex. HOXC13 displays in vitro affinity for other replicative complex proteins; it interacts also in vivo with the same proteins in a cell-cycle-dependent fashion. Chromatin-structure modifying treatments, disturbing origin function, reduce also HOXC13origin interaction. The described interactions are not restricted to a single origin nor to a single homeotic protein (also HOXC10 binds the lamin B2 origin in vivo). Thus, HOX complexes probably contribute in a general, structure-dependent manner, to origin identification and assembly of replicative complexes thereon, in presence of specific chromatin configurations.

Download

Green Fluorescent Proteins Aggregation Dynamics Explored with a Minimalist Coarse Grained Model

Biophysical Journal, 2010

Green Fluorescent Proteins (GFP) are widely used as tags to monitor proteins motion in living cel... more Green Fluorescent Proteins (GFP) are widely used as tags to monitor proteins motion in living cells [1]. GFP diffusional dynamics and optical properties, however, can be influenced by several hardly-controllable factors, such as self-aggregation and crowding in the cytoplasm. A quantitative evaluation of their impact can be of primary importance in the correct interpretation e.g. of FLIM and FRAP data, based on the measurement of diffusional dynamics [2]. A theoretical study of these aspects, however, requires the simulation of a statistical ensemble of GFPs embedded in a realistic cell environment, that is far beyond the capability of standard atomisticbased methods. We shall present a simplified GFP model with the resolution of a single interacting center per amino-acid inspired to previous one-bead minimalist models for proteins and nucleic acids [3,4].The extreme reduction of the degrees of freedom allows us to simulate a large number of GFPs up to macroscopic time scales, and to collect sufficient statistical data for the comparison with experiments. A successful treatment of the internal dynamics is ensured by an accurate parameterization based on the Boltzmann inversion [5]. Particular attention will be devoted to the parameterization of protein-protein interactions in order to accurately simulate GFP aggregation. The cell environment is mimicked including crowder proteins in the system at lower resolution level. Results will be compared to experimental data on aggregation kinetic constants, diffusional constants and FRET experiments. [1] Bizzarri, R. et al. Anal. Bioanal. Chem. 2009, 393, 1107 [2] Chalfie M., Kain S. R. ''Green fluorescent protein: properties, applications and protocols'', Wiley-Interscience (2006) [3] Tozzini, V. Curr. Opin. Struct. Biol. 2005, 15, 144-150

Download

Supercoiling and Local Denaturation of Plasmids with a Minimalist DNA Model

by Fabio Trovato and Valentina Tozzini

Journal of Physical Chemistry B, 2008

Download

Genetic Algorithm Optimization of Force Field Parameters: Application to a Coarse-Grained Model of RNA

by Fabio Trovato and Valentina Tozzini

Determining force field parameters for molecular dynamics simulations of reduced models of biomol... more Determining force field parameters for molecular dynamics simulations of reduced models of biomolecules is a long, troublesome, and exhaustive process that is often performed manually. To improve this parametrization procedure we apply a continuous-space Genetic Algorithm (GA). GA is implemented to optimize parameters of a coarse-grained potential energy function of ribonucleic acid (RNA) molecules. The parameters obtained using GA are correctly reproducing the dynamical behavior of an RNA helix and other RNA tertiary motifs. Therefore, GA can be a useful tool for force field parametrization of the effective potentials in coarse-grained molecular models.