534 research outputs found
Reading the three--dimensional structure of a protein from its amino acid sequence
No full textWhile all the information required for the folding of a protein is contained in its amino acid sequence, one has not yet learned how to extract this information to predict the detailed, biological active, three-dimensional structure of a protein whose sequence is known. Using insight obtained from lattice model simulations of the folding of small proteins (fewer than 100 residues), in particular of the fact that this phenomenon is essentially controlled by conserved contacts (Mirny et al., Proc Natl Acad Sci USA 1995;92:1282) among (few) strongly interacting ("hot") amino acids (Tiana et al., J Chem Phys 1998;108:757-761), which also stabilize local elementary structures formed early in the folding process and leading to the (postcritical) folding core when they assemble together (Broglia et al., Proc Natl Acad Sci USA 1998;95:12930, Broglia & Tiana, J Chem Phys 2001;114:7267), we have worked out a successful strategy for reading the three-dimensional structure of lattice model-designed proteins from the knowledge of only their amino acid sequence and of the contact energies among the amino acids
On the application of the single-phase level set method to naval hydrodynamic flows
No full textThe application of the single-phase level set approach to the numerical simulations of three-dimensional free surface flows around complex geometries, at both non-breaking and breaking regimes is presented. In this approach only the liquid phase is simulated and the level set function is used as tracking device to locate the free surface position. The extrapolation of the solution in the dummy points in the gaseous phase is such that second-order accuracy is maintained also in the points adjacent to the free surface; the time evolution of the level set function and the re-initialization step have been merged so to get a function which is a distance function everywhere, and satisfies, at the same time, the kinematic condition on the free surface. The implementation of this technique into a general purpose Reynolds averaged Navier-Stokes (RANS) equations solver developed at INSEAN [Di Mascio A, Broglia R, Favini B. A Second Order Godunov-type Scheme for Naval Hydrodynamics. Kluwer Academic/Plenum Publishers; 2001, p. 253-61], is described in details; capabilities of the algorithm in dealing with non-breaking and breaking flows in the naval hydrodynamic context will be demonstrated by using a submerged hydrofoil and two different ship hulls in straight course as test cases. Comparisons with both experimental data and numerical surface fitting computations are presented; convergence properties of the algorithm, as well as validation and verification assessment will be also discussed. © 2006 Elsevier Ltd. All rights reserved
Turning ability analysis of a fully appended twin screw vessel by CFD. Part II: Single vs. twin rudder configuration
No full textIn the present paper, the analysis of the turning capability of the naval supply vessel presented in Part I (Broglia et al., 2015) is continued with different stern appendages, namely twin rudder and centreline skeg. The main purpose of the analysis is to assess the capability of an in-house CFD tool in capturing the different manoeuvring characteristics of the ship hulls; the test case is challenging, as the difference between the two configurations lies in the complex flow structure related to rudder-propeller interactions. Moreover, although the twin rudder solution slightly improves the poor course keeping ability of the original vessel, the course stability remains poor and, consequently, large lateral motions and drift angle have to be expected during the manoeuvre. The manoeuvring capabilities of the new configuration are discussed and compared with the single rudder configuration, focusing on the nature of the hydrodynamic forces and moments acting on the main hull and appendages during the transient and stabilized phases of the manoeuvre. Emphasis will be also given to the different contributions of the propulsion system in the twin rudder configuration, that results from the different rudder-propeller interaction
Correlation energy contribution to nuclear masses
No full textDuring the last few years, much effort has been made to develop a microscopic description of the nuclear masses based on mean field theory. The accuracy achieved, when phenomenological parameters are added to take specific effects into account (Wigner term, cut-off in pairing space, etc.), leads to a rms of 0.6–0.7 MeV [S. Goriely, F. Tondeur, J.M. Pearson, Atom Data Nucl. Data Tables 77 (2001) 311] (see also [M. Bender, P.H. Heenen, P.G. Reinhard, Rev. Modern Phys. 75 (2003) 121]). We present evidence that further progress can be made by taking into account medium polarization effects associated with surface and pairing vibrations [S. Baroni, M. Armati, F. Barranco, R.A. Broglia, G. Colò, G. Gori, E. Vigezzi, J. Phys. G: Nucl. Part. Phys. 30 (2004) 1353; S. Baroni, F. Barranco, P.F. Bortignon, R.A. Broglia, G. Colò, E. Vigezzi, Phys. Rev. C 74 (2006) 024305] (see also [M. Bender, G.F. Bertsch, P.-H. Heenen, Phys. Rev. C 73 (2006) 034322])
From phase transitions in finite systems to protein folding and non-conventional drug design
No full textSome of the paradigms emerging from the study of the phenomena of phase transitions in finite many-body systems, like, e.g., the atomic nuclues, can be used at profit to solve the protein folding problem (how does a linear sequence of amino acids, immersed in the solvent, code for a unique, biological active, three-dimensional native structure of the protein?), within the framework of simple (although not oversimplified) models. Also to design non-conventional drugs which do not create resistance (do not induce mutations in the virus or bacteria expressing the protein). The application of these concepts to the design of inhibitors of the HIV-1-PR, an enzyme which plays a central role in the life cycle of the HIV virus will be illustrated in terms of all-atom simulations and in vitro experimental results
Hierarchy of Events in the folding of model proteins
No full textThe protein folding problem, i.e. prediction of the detailed three-dimensional structure of a known real protein sequence is discussed. All the information about the structure is present in the amino acid sequence. Proteins under normal condition will fold to their native state. Good folder sequence are charcterized by large gap between the energy sequence. The local elementary structures are formed at the very early stages of the composition process. The designed sequence displays same folding mechanism
Statistical Analysis of Native Contact Formation in the Folding of Designed Model Proteins
No full textThe time evolution of native bonds formation probability was studied for designed sequences which fold fast into the native conformation. The native bonds formed was classified into three groups. These are: local, fast forming highly stable native bonds produced from strongly interacting amino acid of the protein; nonlocal bonds formed late in the folding process simultaneously with the folding nucleus and has essentially similar strongly interacting amino acids already found in the fast bonds; and the rest of the native bonds which are subordinate, to a large extent, to that of the strong local and nonlocal native contacts
The molecular evolution of HIV-1 protease simulated at atomic detail
No full textProgress in understanding protein folding allows to simulate, with atomic detail, the evolution of amino-acid sequences folding to a given native conformation. A particularly attractive example is the HIV-1 protease, main target of therapies to fight AIDS, which under drug pressure is able to develop resistance within few months from the starting of therapy. By comparing the results of simulations of the evolution of the protease with the corresponding proteomic data, one can approximately determine the value of the associated evolution pressure under which the enzyme has become and, as a consequence, map out the energy landscape in sequence space of the HIV-1 protease. It is found that there are several families of sequences folding to the native conformations of the enzyme. Each of these families are characterized by different sets of highly conserved ( hot) amino acids which play a critical role in the folding and stability of the protease. There are two main possibilities for the virus to move from one family to a different one: (a) in a single generation, through the concerted mutations of the hot amino acids, a highly unlikely event, (b) through a folding path (if it exists), again a very improbable event. In fact, the number of generations needed by the virus to change stepwise its sequence from one family to another is astronomically large. These results point to the hot segments of the protease as promising targets for a nonconventional inhibition strategy, likely not to create resistance
Analysis of the flow around a manoeuvring VLCC
No full textThis work describes the numerical simulation of a turning circle manoeuvre performed by the MOERI KVLCC2 induced by the rotation of the rudder. To this purpose, the Navier-Stokes equations are integrated, the hydrodynamical forces acting on the hull are computed and the hull is moved at each time step according to the rigid body equations. Because of the scarceness of experimental results for this kind of simulations, the validation of the proposed method is postponed to the oral presentation when the data from the SIM- MAN 2008 Workshop (http://www.simman2008.dk/) will be available. Copyright © 2008 by ASME
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