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Biomedical subjects

Amos Maritan

Publications and source records attributed to Amos Maritan.

At least 19 recordsLinked to original sources
PubMed2004

Geometrical model for the native-state folds of proteins.

We recently introduced a physical model [T.X. Hoang, A. Trovato, F. Seno, J.R. Banavar, A. Maritan, Geometry and symmetry pre-sculpt the free energy landscape of proteins. Proc. Natl. Acad. Sci. U. S. A. 101 (2004) 7960-7964, J.R. Banavar, T.X. Hoang, A. Maritan, F. Seno, A. Trovato, A unified perspective on proteins-a physics approach. Phys. Rev., E 70 (2004) 041905] for proteins which incorporates, in an approximate manner, several key features such as the inherent anisotropy of a chain molecule, the geometrical and energetic constraints placed by the hydrogen bonds and sterics, and the role played by hydrophobicity. Within this framework, marginally compact conformations resembling the native state folds of proteins emerge as broad competing minima in the free energy landscape even for a homopolymer. Here we show how the introduction of sequence heterogeneity using a simple scheme of just two types of amino acids, hydrophobic (H) and polar (P), and sequence design allows a selected putative native fold to become the free energy minimum at low temperature. The folding transition exhibits thermodynamic cooperativity, if one neglects the degeneracy between two different low energy conformations sharing the same fold topology.

Hydrogen Bonding↗
PubMed2004

Lattice tube model of proteins.

We present a new lattice model for proteins that incorporates a tubelike anisotropy by introducing a preference for mutually parallel alignments in the conformations. The model is demonstrated to capture many aspects of real proteins.

Anisotropy↗
PubMed2004

Unified perspective on proteins: a physics approach.

We study a physical system which, while devoid of the complexity one usually associates with proteins, nevertheless displays a remarkable array of proteinlike properties. The constructive hypothesis that this striking resemblance is not accidental not only leads to a unified framework for understanding protein folding, amyloid formation, and protein interactions but also has implications for natural selection.

Binding Sites↗
PubMed2004

Simulations of action of DNA topoisomerases to investigate boundaries and shapes of spaces of knots.

The configuration space available to randomly cyclized polymers is divided into subspaces accessible to individual knot types. A phantom chain utilized in numerical simulations of polymers can explore all subspaces, whereas a real closed chain forming a figure-of-eight knot, for example, is confined to a subspace corresponding to this knot type only. One can conceptually compare the assembly of configuration spaces of various knot types to a complex foam where individual cells delimit the configuration space available to a given knot type. Neighboring cells in the foam harbor knots that can be converted into each other by just one intersegmental passage. Such a segment-segment passage occurring at the level of knotted configurations corresponds to a passage through the interface between neighboring cells in the foamy knot space. Using a DNA topoisomerase-inspired simulation approach we characterize here the effective interface area between neighboring knot spaces as well as the surface-to-volume ratio of individual knot spaces. These results provide a reference system required for better understanding mechanisms of action of various DNA topoisomerases.

Bacteriophage T4↗
PubMed2004

What can one learn from experiments about the elusive transition state?

We present the results of an exact analysis of a model energy landscape of a protein to clarify the idea of the transition state and the physical meaning of the phi values determined in protein engineering experiments. We benchmark our findings to various theoretical approaches proposed in the literature for the identification and characterization of the transition state.

Models, Molecular↗
PubMed2004

Stochastic model for the species abundance problem in an ecological community.

We propose a model based on coupled multiplicative stochastic processes to understand the dynamics of competing species in an ecosystem. This process can be conveniently described by a Fokker-Planck equation. We provide an analytical expression for the marginalized stationary distribution. Our solution is found in excellent agreement with numerical simulations and compares rather well with observational data from tropical forests.

Animals↗
PubMed2004

Geometry and symmetry presculpt the free-energy landscape of proteins.

We present a simple physical model that demonstrates that the native-state folds of proteins can emerge on the basis of considerations of geometry and symmetry. We show that the inherent anisotropy of a chain molecule, the geometrical and energetic constraints placed by the hydrogen bonds and sterics, and hydrophobicity are sufficient to yield a free-energy landscape with broad minima even for a homopolymer. These minima correspond to marginally compact structures comprising the menu of folds that proteins choose from to house their native states in. Our results provide a general framework for understanding the common characteristics of globular proteins.

Anisotropy↗
PubMed2004

Accurate and efficient description of protein vibrational dynamics: comparing molecular dynamics and Gaussian models.

Current all-atom potential based molecular dynamics (MD) allows the identification of a protein's functional motions on a wide-range of timescales, up to few tens of nanoseconds. However, functional, large-scale motions of proteins may occur on a timescale currently not accessible by all-atom potential based MD. To avoid the massive computational effort required by this approach, several simplified schemes have been introduced. One of the most satisfactory is the Gaussian network approach based on the energy expansion in terms of the deviation of the protein backbone from its native configuration. Here, we consider an extension of this model that captures in a more realistic way the distribution of native interactions due to the introduction of effective side-chain centroids. Since their location is entirely determined by the protein backbone, the model is amenable to the same exact and computationally efficient treatment as previous simpler models. The ability of the model to describe the correlated motion of protein residues in thermodynamic equilibrium is established through a series of successful comparisons with an extensive (14 ns) MD simulation based on the AMBER potential of HIV-1 protease in complex with a peptide substrate. Thus, the model presented here emerges as a powerful tool to provide preliminary, fast yet accurate characterizations of protein near-native motion.

Computer Simulation↗
PubMed2004

Recognition of coarse-grained protein tertiary structure.

A model of the protein backbone is considered in which each residue is characterized by the location of its C(alpha) atom and one of a discrete set of conformal (phi, psi) states. We investigate the key differences between a description that offers a locally precise fit to known backbone structures and one that provides a globally accurate fit to protein structures. Using a statistical scoring scheme and threading, a protein's local best-fit conformation is highly recognizable, but its global structure cannot be directly determined from an amino acid sequence. The incorporation of information about the conformal states of neighboring residues along the chain allows one to accurately translate the local structure into a global structure. We present a two-step algorithm, which recognizes up to 95% of the tested protein native-state structures to within a 2.5 A root mean square deviation.

Algorithms↗
PubMed2004

Network structures from selection principles.

We present an analysis of the topologies of a class of networks which are optimal in terms of the requirements of having as short a route as possible between any two nodes while yet keeping the congestion in the network as low as possible. Strikingly, we find a variety of distinct topologies and novel phase transitions between them on varying the number of links per node. Our results suggest that the emergence of the topologies observed in nature may arise both from growth mechanisms and the interplay of dynamical mechanisms with a selection process.

Journal Article↗
PubMed2004

Scale-free behavior and universality in random fragmentation and aggregation.

Two distinct mechanisms underlying the existence of power-law distributions are presented: the distribution is stationary under the process of merging and splitting of classes and the distribution of the entities under study is invariant under changes of the classification scheme. We provide an explanation for the ubiquitous inverse n relationship in the species abundance relationship in ecology and the 1/n(2) distribution of company sizes based on the minimum impact principle.

Journal Article↗
PubMed2004

Neutral theory: the stability of forest biodiversity.

The unified neutral theory of biodiversity and biogeography provides a dynamic null hypothesis for the assembly of natural communities. It is also useful for understanding the influence of speciation, extinction, dispersal and ecological drift on patterns of relative species abundance, species-area relationships and phylogeny. Clark and McLachlan argue that neutral drift is inconsistent with the palaeorecord of stability in fossil pollen assemblages of the Holocene forests of southern Canada. We show here that their analysis is based on a partial misunderstanding of neutral theory and that their data alone cannot unambiguously test its validity.

Biodiversity↗
PubMed2003

Neutral theory and relative species abundance in ecology.

The theory of island biogeography asserts that an island or a local community approaches an equilibrium species richness as a result of the interplay between the immigration of species from the much larger metacommunity source area and local extinction of species on the island (local community). Hubbell generalized this neutral theory to explore the expected steady-state distribution of relative species abundance (RSA) in the local community under restricted immigration. Here we present a theoretical framework for the unified neutral theory of biodiversity and an analytical solution for the distribution of the RSA both in the metacommunity (Fisher's log series) and in the local community, where there are fewer rare species. Rare species are more extinction-prone, and once they go locally extinct, they take longer to re-immigrate than do common species. Contrary to recent assertions, we show that the analytical solution provides a better fit, with fewer free parameters, to the RSA distribution of tree species on Barro Colorado Island, Panama, than the lognormal distribution.

Animals↗
PubMed2003

Assembly of protein tertiary structures from secondary structures using optimized potentials.

We present a simulated annealing-based method for the prediction of the tertiary structures of proteins given knowledge of the secondary structure associated with each amino acid in the sequence. The backbone is represented in a detailed fashion whereas the sidechains and pairwise interactions are modeled in a simplified way, following the LINUS model of Srinivasan and Rose. A perceptron-based technique is used to optimize the interaction potentials for a training set of three proteins. For these proteins, the procedure is able to reproduce the tertiary structures to below 3 A in root mean square deviation (rmsd) from the PDB targets. We present the results of tests on twelve other proteins. For half of these, the lowest energy decoy has a rmsd from the native state below 6 A and, in 9 out of 12 cases, we obtain decoys whose rmsd from the native states are also well below 5 A.

Amino Acids↗
PubMed2003

Global protein function prediction from protein-protein interaction networks.

Determining protein function is one of the most challenging problems of the post-genomic era. The availability of entire genome sequences and of high-throughput capabilities to determine gene coexpression patterns has shifted the research focus from the study of single proteins or small complexes to that of the entire proteome. In this context, the search for reliable methods for assigning protein function is of primary importance. There are various approaches available for deducing the function of proteins of unknown function using information derived from sequence similarity or clustering patterns of co-regulated genes, phylogenetic profiles, protein-protein interactions (refs. 5-8 and Samanta, M.P. and Liang, S., unpublished data), and protein complexes. Here we propose the assignment of proteins to functional classes on the basis of their network of physical interactions as determined by minimizing the number of protein interactions among different functional categories. Function assignment is proteome-wide and is determined by the global connectivity pattern of the protein network. The approach results in multiple functional assignments, a consequence of the existence of multiple equivalent solutions. We apply the method to analyze the yeast Saccharomyces cerevisiae protein-protein interaction network. The robustness of the approach is tested in a system containing a high percentage of unclassified proteins and also in cases of deletion and insertion of specific protein interactions.

Algorithms↗