Hydrophobicity and Unique Folding of Selected Polymers

In suitable environments, proteins, nucleic acids and certain synthetic polymers fold into unique conformations. This work shows that it is possible to construct lattice models of foldable heteropolymers by expressing the energy only in terms of individual properties of monomers, such as the exposure to the solvent and the steric factor.Comment: 5 pages, RevTe

Recovery of Protein Structure from Contact Maps

We present an efficient algorithm to recover the three dimensional structure of a protein from its contact map representation. First we show that when a physically realizable map is used as target, our method generates a structure whose contact map is essentially similar to the target. Furthermore, the reconstructed and original structures are similar up to the resolution of the contact map representation. Next we use non-physical target maps, obtained by corrupting a physical one; in this case our method essentially recovers the underlying physical map and structure. Hence our algorithm will help to fold proteins, using dynamics in the space of contact maps. Finally we investigate the manner in which the quality of the recovered structure degrades when the number of contacts is reduced.Comment: 27 pages, RevTex, 12 figures include

Structurally constrained protein evolution: results from a lattice simulation

We simulate the evolution of a protein-like sequence subject to point mutations, imposing conservation of the ground state, thermodynamic stability and fast folding. Our model is aimed at describing neutral evolution of natural proteins. We use a cubic lattice model of the protein structure and test the neutrality conditions by extensive Monte Carlo simulations. We observe that sequence space is traversed by neutral networks, i.e. sets of sequences with the same fold connected by point mutations. Typical pairs of sequences on a neutral network are nearly as different as randomly chosen sequences. The fraction of neutral neighbors has strong sequence to sequence variations, which influence the rate of neutral evolution. In this paper we study the thermodynamic stability of different protein sequences. We relate the high variability of the fraction of neutral mutations to the complex energy landscape within a neutral network, arguing that valleys in this landscape are associated to high values of the neutral mutation rate. We find that when a point mutation produces a sequence with a new ground state, this is likely to have a low stability. Thus we tentatively conjecture that neutral networks of different structures are typically well separated in sequence space. This results indicates that changing significantly a protein structure through a biologically acceptable chain of point mutations is a rare, although possible, event.Comment: added reference, to appear on European Physical Journal

Folding Lennard-Jones proteins by a contact potential

We studied the possibility to approximate a Lennard Jones interaction by a pairwise contact potential. First we used a Lennard-Jones potential to design off-lattice, protein-like heteropolymer sequences, whose lowest energy (native) conformations were then identified by Molecular Dynamics. Then we turned to investigate whether one can find a pairwise contact potential, whose ground states are the contact maps associated with these native conformations. We show that such a requirement cannot be satisfied exactly - i.e. no such contact parameters exist. Nevertheless, we found that one can find contact energy parameters for which an energy minimization procedure, acting in the space of contact maps, yields maps whose corresponding structures are close to the native ones. Finally we show that when these structures are used as the initial point of a Molecular Dynamics energy minimization process, the correct native folds are recovered with high probability.Comment: submitted to "Proteins: Structure, Function, and Genetics

Statistical properties of contact vectors

We study the statistical properties of contact vectors, a construct to characterize a protein's structure. The contact vector of an N-residue protein is a list of N integers n_i, representing the number of residues in contact with residue i. We study analytically (at mean-field level) and numerically the amount of structural information contained in a contact vector. Analytical calculations reveal that a large variance in the contact numbers reduces the degeneracy of the mapping between contact vectors and structures. Exact enumeration for lengths up to N=16 on the three dimensional cubic lattice indicates that the growth rate of number of contact vectors as a function of N is only 3% less than that for contact maps. In particular, for compact structures we present numerical evidence that, practically, each contact vector corresponds to only a handful of structures. We discuss how this information can be used for better structure prediction.Comment: 20 pages, 6 figure

Codici dell'Argiropulo tra gli Utinenses Graeci

pp.289-297Dieci degli Utinenses Graeci, per metà codici umanistici, contenenti testi o commenti aristotelici, per l’altra metà bizantini (datati dal X al XIV secolo) di contenuto patristico o ascetico, rimontano a una singola collezione libraria del primo ’500, quella dell’illustre cardinale veneziano e patriarca di Aquileia Domenico Grimani, forse la maggiore biblioteca europea dell’epoca: di questi almeno otto (Utinn. 254, 255, 256II, 258, 260, 261, 262, 263) si trovavano già associati nella vasta biblioteca di Giovanni Pico della Mirandola, che dopo la sua morte fu acquistata, nel 1498 dal Grimani. È possibile che i tre codici aristotelici (264, 265, 266) – a Firenze con Pico, a Roma col Grimani, a Venezia a San Giovanni di Castello, poi presso Antonio Capello, infine, col patriarca Dolfin, a Udine, nella pubblica biblioteca inaugurata nel 1711 – fossero accomunati fin dall’‘origine’ umanistica, presso uno dei protagonisti del passaggio di consegne culturale tra Bisanzio e l’Europa moderna: Giovanni Argiropulo.Ten out of Utinenses Graeci, half humanistic codes, with Aristotelian texts or comments, the other half Byzantine (dating from the tenth to fourteenth centuries) with patristic or ascetic content, back to a single book collection of the first '500, that of illustrious Venetian cardinal and patriarch of Aquileia Domenico Grimani, perhaps the largest library of the Europe in that age: of these, at least eight (Utinn. 254, 255, 256II, 258, 260, 261, 262, 263) were already associated in the vast library of Giovanni Pico della Mirandola, who after his death it was purchased in 1498 by Grimani. It is possible that the three Aristotelian codes (264, 265, 266) – in Florence with Pico, in Rome with Grimani, in Venice at San Giovanni di Castello, then at Antonio Capello, finally, with the patriarch Dolfin, in Udin, in the public library inaugurated in 1711 - were united from the humanistic origin, at one of the protagonists of the cultural hand over between Byzantium and modern Europe: Johannes Argiropulos