Integration of navigation and action selection functionalities in a computational model of cortico-basal ganglia-thalamo-cortical loops

This article describes a biomimetic control architecture affording an animat both action selection and navigation functionalities. It satisfies the survival constraint of an artificial metabolism and supports several complementary navigation strategies. It builds upon an action selection model based on the basal ganglia of the vertebrate brain, using two interconnected cortico-basal ganglia-thalamo-cortical loops: a ventral one concerned with appetitive actions and a dorsal one dedicated to consummatory actions. The performances of the resulting model are evaluated in simulation. The experiments assess the prolonged survival permitted by the use of high level navigation strategies and the complementarity of navigation strategies in dynamic environments. The correctness of the behavioral choices in situations of antagonistic or synergetic internal states are also tested. Finally, the modelling choices are discussed with regard to their biomimetic plausibility, while the experimental results are estimated in terms of animat adaptivity

Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations

The electron density and electrostatic potential in an aldose reductase holoenzyme complex have been studied by density functional theory (DFT) and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway by using NADPH as a cofactor. The ultra-high resolution of the diffraction data and the low thermal-displacement parameters of the structure allow accurate atomic positions and an experimental charge density analysis. Based on the x-ray structural data, order-N DFT calculations have been performed on subsets of up to 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with the program MOPRO by using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids. Electrostatic potentials calculated from the charge density database, the preliminary experimental electron density analysis, DFT computations, and atomic charges taken from the AMBER software dictionary are compared. The electrostatic complementarity between the cofactor NADP+ and the active site shows up clearly. The anchoring of the inhibitor is due mainly to hydrophobic forces and to only two polar interaction sites within the enzyme cavity. The potentials calculated by x-ray and DFT techniques agree reasonably well. At the present stage of the refinement, the potentials obtained directly from the database are in excellent agreement with the experimental ones. In addition, these results demonstrate the significant contribution of electron lone pairs and of atomic polarization effects to the host and guest mechanism.Instituto de Física de Líquidos y Sistemas BiológicosFacultad de Ciencias Exacta

Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations

The electron density and electrostatic potential in an aldose reductase holoenzyme complex have been studied by density functional theory (DFT) and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway by using NADPH as a cofactor. The ultra-high resolution of the diffraction data and the low thermal-displacement parameters of the structure allow accurate atomic positions and an experimental charge density analysis. Based on the x-ray structural data, order-N DFT calculations have been performed on subsets of up to 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with the program MOPRO by using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids. Electrostatic potentials calculated from the charge density database, the preliminary experimental electron density analysis, DFT computations, and atomic charges taken from the AMBER software dictionary are compared. The electrostatic complementarity between the cofactor NADP+ and the active site shows up clearly. The anchoring of the inhibitor is due mainly to hydrophobic forces and to only two polar interaction sites within the enzyme cavity. The potentials calculated by x-ray and DFT techniques agree reasonably well. At the present stage of the refinement, the potentials obtained directly from the database are in excellent agreement with the experimental ones. In addition, these results demonstrate the significant contribution of electron lone pairs and of atomic polarization effects to the host and guest mechanism.Instituto de Física de Líquidos y Sistemas BiológicosFacultad de Ciencias Exacta

Ultrahigh-resolution crystallography and related electron density and electrostatic properties in proteins

Ultrahigh-resolution protein diffraction data allow valence electron density modelling and calculations of experimental electrostatic properties. Protein–ligand interaction energy may therefore be estimated

At the Interface of Isomorphous Behavior in a 3 × 3 Isomer Grid of Monochlorobenzamides: Analyses of the Interaction Landscapes via Contact Enrichment Studies

International audienceThe physicochemical properties of a 33 isomer grid of mono-chlorobenzamides (Clxx) are reported with comprehensive studies of their crystal structures and interaction environments (Clx = para-/meta-/ortho-chlorobenzoyl and x = para-/meta-/ortho-aminopyridine substitutions). The nine compound Clxx series was synthesised from the three p-/m-/o-chlorobenzoyl chlorides and three p-/m-/o-aminopyridine isomers using standard synthetic procedures. Clxx exhibits some similarities to the related Fxx and Brxx congeners e.g. the isomorphous behaviour of Clpp (para-Chloro-N'-(para-pyridyl)benzamide) with several close relatives, and there are five isomorphous pairs of Clxx and Brxx crystal structures. Notably Clmp and Clpm both crystallise with Z'=4 in space group P but show important differences. The overall lack of isomers crystallising with solvate molecules is noteworthy, except for Clmm(H 2 O). In all Clxx crystal structures, strong N-H…N hydrogen bonds form, however, Clpo also crystallises as the unexpected Clpo_O polymorph with N-H…O=C intermolecular hydrogen bonding. The Clxo triad (with ortho-pyridines) exhibits the expected cyclic N-H…N dimer formation with R 2 2 (8) hydrogen bonded rings. The H C atom type, forming weak C-H…Cl hydrogen bonds, is the only favoured interaction partner of chlorine in Clxx. Conformational analyses (gas phase) together with crystal contact enrichment studies place Clxx in context and at the interface of hydrogen and halogen bonding interactions, though strong hydrogen bonding dominates. In Clxx the interaction energies with nearest neighbours are shown to contribute to most of the lattice electrostatic energies. The melting temperatures T m show correlation with both molecular symmetry (Carnelley's rule) and total electrostatic energy of the weak interactions; in addition, these T m values can be well predicted from a linear fit combining both descriptors. In Clxx, N-H…N hydrogen bonds dominate, largely in the absence of solvates, and with five Clxx forming isomorphous pairs with Brxx analogues; Clpp being isomorphous with several close benzamide relatives. Analysis of T m reveals correlations involving both symmetry and electrostatic energies

Analyzing interactions between navigation strategies using a computational model of action selection

For animals as well as for humans, the hypothesis of multiple memory systems involved in different navigation strategies is supported by several biological experiments. However, due to technical limitations, it remains difficult for experimentalists to elucidate how these neural systems interact. We present how a computational model of selection between navigation strategies can be used to analyse phenomena that cannot be directly observed in biological experiments. We reproduce an experiment where the rat's behaviour is assumed to be ruled by two different navigation strategies (a cue-guided and a map-based one). Using a modelling approach, we can explain the experimental results in terms of interactions between these systems, either competing or cooperating at specific moments of the experiment. Modelling such systems can help biological investigations to explain and predict the animal behaviour

Electrostatic complementarity in an aldose reductase complex from ultra-high-resolution crystallography and first-principles calculations

The electron density and electrostatic potential in an aldose reductase holoenzyme complex have been studied by density functional theory (DFT) and diffraction methods. Aldose reductase is involved in the reduction of glucose in the polyol pathway by using NADPH as a cofactor. The ultra-high resolution of the diffraction data and the low thermal-displacement parameters of the structure allow accurate atomic positions and an experimental charge density analysis. Based on the x-ray structural data, order-N DFT calculations have been performed on subsets of up to 711 atoms in the active site of the molecule. The charge density refinement of the protein was performed with the program MOPRO by using the transferability principle and our database of charge density parameters built from crystallographic analyses of peptides and amino acids. Electrostatic potentials calculated from the charge density database, the preliminary experimental electron density analysis, DFT computations, and atomic charges taken from the AMBER software dictionary are compared. The electrostatic complementarity between the cofactor NADP+ and the active site shows up clearly. The anchoring of the inhibitor is due mainly to hydrophobic forces and to only two polar interaction sites within the enzyme cavity. The potentials calculated by x-ray and DFT techniques agree reasonably well. At the present stage of the refinement, the potentials obtained directly from the database are in excellent agreement with the experimental ones. In addition, these results demonstrate the significant contribution of electron lone pairs and of atomic polarization effects to the host and guest mechanism.Instituto de Física de Líquidos y Sistemas BiológicosFacultad de Ciencias Exacta

Syn-tectonic, meteoric water-derived carbonation of the New Caledonia peridotite nappe

International audienceExceptional outcrops recently exposed in the Koniambo massif allow the study of the serpentine sole of the peridotite nappe of New Caledonia (southwest Pacific Ocean). Many magnesite veins are observed, with characteristics indicating that they were emplaced during pervasive top-to-the-southwest shear deformation. The oxygen isotope composition of magnesite is homogeneous (27.4‰ < δ18O < 29.7‰), while its carbon isotope composition varies widely (−16.7‰ < δ13C < −8.5‰). These new data document an origin of magnesite from meteoric fluids. Laterization on top of the peridotite nappe and carbonation along the sole appear to represent complementary records of meteoric water infiltration. Based on the syn-kinematic character of magnesite veins, we propose that syn-laterization tectonic activity has enhanced water infiltration, favoring the exportation of leached elements like Mg, which has led to widespread carbonation along the serpentine sole. This calls for renewed examination of other magnesite-bearing ophiolites worldwide in order to establish whether active tectonics is commonly a major agent for carbonation