Guido Tiana - Academia.edu (original) (raw)
Papers by Guido Tiana
Physical review. E, Statistical, nonlinear, and soft matter physics, 2015
Biopolymers are characterized by heterogeneous interactions, and usually perform their biological... more Biopolymers are characterized by heterogeneous interactions, and usually perform their biological tasks forming contacts within domains of limited size. Combining polymer theory with a replica approach, we study the scaling properties of the probability of contact formation in random heteropolymers as a function of their linear distance. It is found that, close to or above the θ point, it is possible to define a contact probability which is typical (i.e., "self-averaging") for different realizations of the heterogeneous interactions, and which displays an exponential cutoff, dependent on temperature and on the interaction range. In many cases this cutoff is comparable with the typical sizes of domains in biopolymers. While it is well known that disorder causes interesting effects at low temperature, the behavior elucidated in the present study is an example of a nontrivial effect at high temperature.
The Journal of chemical physics, Jan 21, 2014
The current capacity of computers makes it possible to perform simulations of small systems with ... more The current capacity of computers makes it possible to perform simulations of small systems with portable, explicit-solvent potentials achieving high degree of accuracy. However, simplified models must be employed to exploit the behavior of large systems or to perform systematic scans of smaller systems. While powerful algorithms are available to facilitate the sampling of the conformational space, successful applications of such models are hindered by the availability of simple enough potentials able to satisfactorily reproduce known properties of the system. We develop an interatomic potential to account for a number of properties of proteins in a computationally economic way. The potential is defined within an all-atom, implicit solvent model by contact functions between the different atom types. The associated numerical values can be optimized by an iterative Monte Carlo scheme on any available experimental data, provided that they are expressible as thermal averages of some con...
The Journal of Chemical Physics, 2013
The primary structure of proteins, that is their sequence, represents one of the most abundant se... more The primary structure of proteins, that is their sequence, represents one of the most abundant set of experimental data concerning biomolecules. The study of correlations in families of co-evolving proteins by means of an inverse Ising-model approach allows to obtain information on their native conformation. Following up on a recent development along this line, we optimize the algorithm to calculate effective energies between the residues, validating the approach both back-calculating interaction energies in a model system, and predicting the free energies associated to mutations in real systems. Making use of these effective energies, we study the networks of interactions which stabilizes the native conformation of some well-studied proteins, showing that it display different properties than the associated contact network. * Electronic address: guido.tiana@unimi.it 1 arXiv:1307.1583v1 [q-bio.BM] 5 Jul 2013
The European Physical Journal B, 2008
With the help of metadynamics it is possible to calculate efficiently the free energy of systems ... more With the help of metadynamics it is possible to calculate efficiently the free energy of systems displaying high energy barriers as a function of few selected "collective variables". In doing this, the contribution of all the other degrees of freedom ("microscopic" variables) is averaged out and, thus, lost. In the following, it is shown that it is possible to calculate the thermal average of these microscopic degrees of freedom during the metadynamics, not loosing this piece of information.
... Immunodeficiency Virus Type-1 Protease Stefano Rusconi 1* , Mirko Lo Cicero 1 , Antonia E Laf... more ... Immunodeficiency Virus Type-1 Protease Stefano Rusconi 1* , Mirko Lo Cicero 1 , Antonia E Laface 2 , Stefania Ferramosca 1 , Eugenio Cesana 2 , Guido Tiana 3 , Davide Provasi 3 , Renato Longhi 4 , Francesca Sirianni 1 , Claus Nielsen 5 , Christian ...
NATO Science for Peace and Security Series B: Physics and Biophysics, 2008
Encyclopedia of Condensed Matter Physics, 2005
Computer Physics Communications, 2015
ABSTRACT Simplified models, including implicit-solvent and coarse-grained models, are useful tool... more ABSTRACT Simplified models, including implicit-solvent and coarse-grained models, are useful tools to investigate the physical properties of biological macromolecules of large size, like protein complexes, large DNA/RNA strands and chromatin fibres. While advanced Monte Carlo techniques are quite efficient in sampling the conformational space of such models, the availability of realistic potentials is still a limitation to their general applicability. The recent development of a computational scheme capable of designing potentials to reproduce any kind of experimental data that can be expressed as thermal averages of conformational properties of the system has partially alleviated the problem. Here we present a program that implements the optimization of the potential with respect to the experimental data through an iterative Monte Carlo algorithm and a rescaling of the probability of the sampled conformations. The Monte Carlo sampling includes several types of moves, suitable for different kinds of system, and various sampling schemes, such as fixed-temperature, replica-exchange and adaptive simulated tempering. The conformational properties whose thermal averages are used as inputs currently include contact functions, distances and functions of distances, but can be easily extended to any function of the coordinates of the system.
Biophysical chemistry, 2014
We have used optical tweezers and molecular dynamics simulations to investigate the unfolding and... more We have used optical tweezers and molecular dynamics simulations to investigate the unfolding and refolding process of a stable monomeric form of HIV-1-protease (PR). We have characterized the behavior under tension of the native state (N), and that of the ensemble of partially folded (PF) conformations the protein visits en route to N, which collectively act as a long-lived state controlling the slow kinetic phase of the folding process. Our results reveal a rich network of unfolding events, where the native state unfolds either in a two-state manner or by populating an intermediate state I, while the PF state unravels through a multitude of pathways, underscoring its structural heterogeneity. Refolding of mechanically denatured HIV-1-PR monomers is also a multiple-pathway process. Molecular dynamics simulations allowed us to gain insight into possible conformations the protein adopts along the unfolding pathways, and provide information regarding possible structural features of th...
Journal of biological physics, 2001
Through systematic studies of lattice Monte Carlo simulations of thefolding of designed heteropol... more Through systematic studies of lattice Monte Carlo simulations of thefolding of designed heteropolymers, we have identified a hierarchy ofspecific elementary phenomena which control the way single domain proteinfold: a) formation of few, local elementary structures, b) creation ofthe (post-critical) folding nucleus through the assemblage together ofthe local elementary structures, c) relaxation of the remaining aminoacids to the native conformation. These results, which are consistentwith a two-state kinetics of the folding of small, single domain proteins,where the local elementary structures and the folding nucleus can be viewedas hidden intermediates along the reaction pathway, provide the basis fora strategy to read the tertiary structure of a protein from its aminoacid sequence.
Journal of biological physics, 2001
A numerical study of the energy landscape of the space of model proteinsequences is carried out. ... more A numerical study of the energy landscape of the space of model proteinsequences is carried out. As a consequence of the heterogeneity of thecontact energies among amino acids, the energy landscape displays a veryrough profile, a behaviour typical of frustrated systems. This givesraise to a hierarchical clustering of low-energy sequences and can have evolutionary consequences.
The Journal of chemical physics, 2004
Explicit simulations of protein evolution, where protein chains are described at a molecular, alt... more Explicit simulations of protein evolution, where protein chains are described at a molecular, although simplified, level provide important information to understand the similarities found to exist between known proteins. The results of such simulations suggest that a number of evolutionary-related quantities, such as the distribution of sequence similarity for structurally similar proteins, are controlled by evolutionary kinetics and do not reflect an equilibrium state. An important result for phylogeny is that a subset of the residues of each protein evolve on a much larger time scale than the other residues.
Physical review. E, Statistical, nonlinear, and soft matter physics, 2015
Biopolymers are characterized by heterogeneous interactions, and usually perform their biological... more Biopolymers are characterized by heterogeneous interactions, and usually perform their biological tasks forming contacts within domains of limited size. Combining polymer theory with a replica approach, we study the scaling properties of the probability of contact formation in random heteropolymers as a function of their linear distance. It is found that, close to or above the θ point, it is possible to define a contact probability which is typical (i.e., "self-averaging") for different realizations of the heterogeneous interactions, and which displays an exponential cutoff, dependent on temperature and on the interaction range. In many cases this cutoff is comparable with the typical sizes of domains in biopolymers. While it is well known that disorder causes interesting effects at low temperature, the behavior elucidated in the present study is an example of a nontrivial effect at high temperature.
The Journal of chemical physics, Jan 21, 2014
The current capacity of computers makes it possible to perform simulations of small systems with ... more The current capacity of computers makes it possible to perform simulations of small systems with portable, explicit-solvent potentials achieving high degree of accuracy. However, simplified models must be employed to exploit the behavior of large systems or to perform systematic scans of smaller systems. While powerful algorithms are available to facilitate the sampling of the conformational space, successful applications of such models are hindered by the availability of simple enough potentials able to satisfactorily reproduce known properties of the system. We develop an interatomic potential to account for a number of properties of proteins in a computationally economic way. The potential is defined within an all-atom, implicit solvent model by contact functions between the different atom types. The associated numerical values can be optimized by an iterative Monte Carlo scheme on any available experimental data, provided that they are expressible as thermal averages of some con...
The Journal of Chemical Physics, 2013
The primary structure of proteins, that is their sequence, represents one of the most abundant se... more The primary structure of proteins, that is their sequence, represents one of the most abundant set of experimental data concerning biomolecules. The study of correlations in families of co-evolving proteins by means of an inverse Ising-model approach allows to obtain information on their native conformation. Following up on a recent development along this line, we optimize the algorithm to calculate effective energies between the residues, validating the approach both back-calculating interaction energies in a model system, and predicting the free energies associated to mutations in real systems. Making use of these effective energies, we study the networks of interactions which stabilizes the native conformation of some well-studied proteins, showing that it display different properties than the associated contact network. * Electronic address: guido.tiana@unimi.it 1 arXiv:1307.1583v1 [q-bio.BM] 5 Jul 2013
The European Physical Journal B, 2008
With the help of metadynamics it is possible to calculate efficiently the free energy of systems ... more With the help of metadynamics it is possible to calculate efficiently the free energy of systems displaying high energy barriers as a function of few selected "collective variables". In doing this, the contribution of all the other degrees of freedom ("microscopic" variables) is averaged out and, thus, lost. In the following, it is shown that it is possible to calculate the thermal average of these microscopic degrees of freedom during the metadynamics, not loosing this piece of information.
... Immunodeficiency Virus Type-1 Protease Stefano Rusconi 1* , Mirko Lo Cicero 1 , Antonia E Laf... more ... Immunodeficiency Virus Type-1 Protease Stefano Rusconi 1* , Mirko Lo Cicero 1 , Antonia E Laface 2 , Stefania Ferramosca 1 , Eugenio Cesana 2 , Guido Tiana 3 , Davide Provasi 3 , Renato Longhi 4 , Francesca Sirianni 1 , Claus Nielsen 5 , Christian ...
NATO Science for Peace and Security Series B: Physics and Biophysics, 2008
Encyclopedia of Condensed Matter Physics, 2005
Computer Physics Communications, 2015
ABSTRACT Simplified models, including implicit-solvent and coarse-grained models, are useful tool... more ABSTRACT Simplified models, including implicit-solvent and coarse-grained models, are useful tools to investigate the physical properties of biological macromolecules of large size, like protein complexes, large DNA/RNA strands and chromatin fibres. While advanced Monte Carlo techniques are quite efficient in sampling the conformational space of such models, the availability of realistic potentials is still a limitation to their general applicability. The recent development of a computational scheme capable of designing potentials to reproduce any kind of experimental data that can be expressed as thermal averages of conformational properties of the system has partially alleviated the problem. Here we present a program that implements the optimization of the potential with respect to the experimental data through an iterative Monte Carlo algorithm and a rescaling of the probability of the sampled conformations. The Monte Carlo sampling includes several types of moves, suitable for different kinds of system, and various sampling schemes, such as fixed-temperature, replica-exchange and adaptive simulated tempering. The conformational properties whose thermal averages are used as inputs currently include contact functions, distances and functions of distances, but can be easily extended to any function of the coordinates of the system.
Biophysical chemistry, 2014
We have used optical tweezers and molecular dynamics simulations to investigate the unfolding and... more We have used optical tweezers and molecular dynamics simulations to investigate the unfolding and refolding process of a stable monomeric form of HIV-1-protease (PR). We have characterized the behavior under tension of the native state (N), and that of the ensemble of partially folded (PF) conformations the protein visits en route to N, which collectively act as a long-lived state controlling the slow kinetic phase of the folding process. Our results reveal a rich network of unfolding events, where the native state unfolds either in a two-state manner or by populating an intermediate state I, while the PF state unravels through a multitude of pathways, underscoring its structural heterogeneity. Refolding of mechanically denatured HIV-1-PR monomers is also a multiple-pathway process. Molecular dynamics simulations allowed us to gain insight into possible conformations the protein adopts along the unfolding pathways, and provide information regarding possible structural features of th...
Journal of biological physics, 2001
Through systematic studies of lattice Monte Carlo simulations of thefolding of designed heteropol... more Through systematic studies of lattice Monte Carlo simulations of thefolding of designed heteropolymers, we have identified a hierarchy ofspecific elementary phenomena which control the way single domain proteinfold: a) formation of few, local elementary structures, b) creation ofthe (post-critical) folding nucleus through the assemblage together ofthe local elementary structures, c) relaxation of the remaining aminoacids to the native conformation. These results, which are consistentwith a two-state kinetics of the folding of small, single domain proteins,where the local elementary structures and the folding nucleus can be viewedas hidden intermediates along the reaction pathway, provide the basis fora strategy to read the tertiary structure of a protein from its aminoacid sequence.
Journal of biological physics, 2001
A numerical study of the energy landscape of the space of model proteinsequences is carried out. ... more A numerical study of the energy landscape of the space of model proteinsequences is carried out. As a consequence of the heterogeneity of thecontact energies among amino acids, the energy landscape displays a veryrough profile, a behaviour typical of frustrated systems. This givesraise to a hierarchical clustering of low-energy sequences and can have evolutionary consequences.
The Journal of chemical physics, 2004
Explicit simulations of protein evolution, where protein chains are described at a molecular, alt... more Explicit simulations of protein evolution, where protein chains are described at a molecular, although simplified, level provide important information to understand the similarities found to exist between known proteins. The results of such simulations suggest that a number of evolutionary-related quantities, such as the distribution of sequence similarity for structurally similar proteins, are controlled by evolutionary kinetics and do not reflect an equilibrium state. An important result for phylogeny is that a subset of the residues of each protein evolve on a much larger time scale than the other residues.