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

Variational principle for theories with dissipation from analytic continuation

The analytic continuation from the Euclidean domain to real space of the one-particle irreducible quantum effective action is discussed in the context of generalized local equilibrium states. Discontinuous terms associated with dissipative behavior are parametrized in terms of a conveniently defined sign operator. A generalized variational principle is then formulated, which allows to obtain causal and real dissipative equations of motion from the analytically continued quantum effective action. Differential equations derived from the implications of general covariance determine the space-time evolution of the temperature and fluid velocity fields and allow for a discussion of entropy production including a local form of the second law of thermodynamics.Comment: 34 pages, improved discussion of dissipative terms in energy momentum tensor, references adde

Summary Report: Project Terra Research Meeting

Developing the conservation of earthen architectural Heritage -- as a science, a field of study, a professional practice, and a social endeavor -- is the overall objective of Project Terra

Structure-based analysis of the ultraspiracle protein and docking studies of putative ligands

The ultraspiracle protein (USP) is the insect ortholog of the mammalian retinoid X receptor (RXR). Fundamental questions concern the functional role of USP as the heterodimerization partner of insect nuclear receptors such as the ecdysone receptor. The crystallographic structures of the ligand binding domain of USPs of Heliothis virescens and Drosophila melanogaster solved recently show that helix 12 is locked in an antagonist conformation raising the question whether USPs could adopt an agonist conformation as observed in RXRα. In order to investigate this hypothesis, a homology model for USP is proposed that allows a structural analysis of the agonist conformation of helix 12 based on the sequence comparison with RXR. For USP, one of the main issues concerns its function and in particular whether its activity is ligand independent or not. The x-ray structures strongly suggest that USP can bind ligands. Putative ligands have therefore been docked in the USP homology model. Juvenile hormones and juvenile hormone analogs were chosen as target ligands for the docking study. The interaction between the ligand and the receptor are examined in terms of the pocket shape as well as in terms of the chemical nature of the residues lining the ligand binding cavity

Enviromental patterns and intermittent cascades

Real environmental flows are non-homogeneous, of fundamental interest is to determine and quantify turbulent diffusion from the available conditions of the flow, because the role of buoyancy and rotation modify the flow topology with often the dominant scale occurring when these two forces are in equilibrium. In geophysical flows both in the Atmosphere and the Ocean, the main forcing occurs at the Rossby deformation Radius with both direct and inverse energy cascades [1,2]. The role of the spectra of steady and decaying turbulence is important as well as its scale to scale conditions, so that a large range of scales has to be taken into account. When mixing and dispersion processes are studied, the behaviour of reactants or pollutants is seen to depend of both the intermittency of the vorticity and energy spectra. If irreversible molecular mixing has to be accounted, the range of scales spans from hundreds of Kilometres to the Bachelor or Kolmogorov sub millimeter scales. It is important to evaluate mixing and compare with oscillating grid experiments, Redondo [3], across a density interface measuring entrainment and grid decaying non steady mixing. These experiments are evaluated and compared with results of a Kinematic simulation model, Castilla [4]. The local vorticity is evaluated confirming the trapping of tracers in the strong vertical regions in 2D flows, but showing also that hyperdiffusion may also occur. Intermittency was evaluated using numerical evaluation of higher order moments in different types of 2D and 3D turbulence.Peer ReviewedPostprint (published version