Can Conformational Changes of Proteins Be Represented in Torsion Angle Space? A Study with Rescaled Ridge Regression

Torsion angles are the natural degrees of freedom of protein structures. The ability to determine torsional variations corresponding to observed changes in Cartesian coordinates is highly valuable, notably to investigate the mechanisms of functional conformational changes or to develop computational models of protein dynamics. This issue is far from trivial in practice since the impact of modifying one torsion angle strongly depends on all other angles, and the compounding effects of small variations in bond lengths and valence angles can completely disrupt a protein fold. We demonstrate that naive strategies, such as directly comparing torsion angles between structures without correcting for variations in bond lengths and valence angles or fitting torsional variations without a proper regularization scheme, fail at producing an adequate representation of conformational changes in internal coordinates. In contrast, rescaled ridge regression, a method recently introduced to regularize multidimensional regressions with correlated explanatory variables, is shown to consistently identify a minimal set of torsion angles variations that closely reproduce changes in Cartesian coordinates. This torsional representation of conformational changes is shown to be robust to the choice of experimental structures. It also provides a better agreement with theoretical models of protein dynamics than the Cartesian representation, regarding notably the predominance of low-frequency normal modes in functional motions and the presence, in predicted equilibrium dynamics, of hints of natural selection for specific functional motions. The software is available at https://github.com/ugobas/tnm.Ministery of Economy, grant BIO2016-79043-P. Research at the CBMSO is facilitated by the Fundacion Ramon Arece

Effective harmonic potentials: insights into the internal cooperativity and sequence-specificity of protein dynamics

The proper biological functioning of proteins often relies on the occurrence of coordinated fluctuations around their native structure, or of wider and sometimes highly elaborated motions. Coarse-grained elastic-network descriptions are known to capture essential aspects of conformational dynamics in proteins, but have so far remained mostly phenomenological, and unable to account for the chemical specificities of amino acids. Here, we propose a method to derive residue- and distance-specific effective harmonic potentials from the statistical analysis of an extensive dataset of NMR conformational ensembles. These potentials constitute dynamical counterparts to the mean-force statistical potentials commonly used for static analyses of protein structures. In the context of the elastic network model, they yield a strongly improved description of the cooperative aspects of residue motions, and give the opportunity to systematically explore the influence of sequence details on protein dynamics.Comment: 10 pages, 5 figures, 1 table ; Supplementary Material (11 pages, 7 figures, 1 table) ; 4 Supplementary tables as plain text file

Protein stability: a single recorded mutation aids in predicting the effects of other mutations in the same amino acid site

Motivation: Accurate prediction of protein stability is important for understanding the molecular underpinnings of diseases and for the design of new proteins. We introduce a novel approach for the prediction of changes in protein stability that arise from a single-site amino acid substitution; the approach uses available data on mutations occurring in the same position and in other positions. Our algorithm, named Pro-Maya (Protein Mutant stAbilitY Analyzer), combines a collaborative filtering baseline model, Random Forests regression and a diverse set of features. Pro-Maya predicts the stability free energy difference of mutant versus wild type, denoted as ΔΔG

Detection of Perturbation Phases and Developmental Stages in Organisms from DNA Microarray Time Series Data

Available DNA microarray time series that record gene expression along the developmental stages of multicellular eukaryotes, or in unicellular organisms subject to external perturbations such as stress and diauxie, are analyzed. By pairwise comparison of the gene expression profiles on the basis of a translation-invariant and scale-invariant distance measure corresponding to least-rectangle regression, it is shown that peaks in the average distance values are noticeable and are localized around specific time points. These points systematically coincide with the transition points between developmental phases or just follow the external perturbations. This approach can thus be used to identify automatically, from microarray time series alone, the presence of external perturbations or the succession of developmental stages in arbitrary cell systems. Moreover, our results show that there is a striking similarity between the gene expression responses to these a priori very different phenomena. In contrast, the cell cycle does not involve a perturbation-like phase, but rather continuous gene expression remodeling. Similar analyses were conducted using three other standard distance measures, showing that the one we introduced was superior. Based on these findings, we set up an adapted clustering method that uses this distance measure and classifies the genes on the basis of their expression profiles within each developmental stage or between perturbation phases

Desiccation cracks provide evidence of lake drying on Mars, Sutton Island member, Murray formation, Gale Crater

Mars Science Laboratory (MSL) Curiosity rover data are used to describe the morphology of desiccation cracks observed in ancient lacustrine strata at Gale crater, Mars, and to interpret their paleoenvironmental setting. The desiccation cracks indicate subaerial exposure of lacustrine facies in the Sutton Island member of the Murray formation. In association with ripple cross-stratification and possible eolian cross-bedding, these facies indicate a transition from longer-lived perennial lakes recorded by older strata to younger lakes characterized by intermittent exposure. The transition from perennial to episodically exposed lacustrine environments provides evidence for local to regional climate change that can help constrain Mars climate models

PoPMuSiC 2.1: a web server for the estimation of protein stability changes upon mutation and sequence optimality

ABSTRACT:Journal ArticleSCOPUS: ar.jinfo:eu-repo/semantics/publishe

The SuperCam Instrument Suite on the Mars 2020 Rover: Science Objectives and Mast-Unit Description

On the NASA 2020 rover mission to Jezero crater, the remote determination of the texture, mineralogy and chemistry of rocks is essential to quickly and thoroughly characterize an area and to optimize the selection of samples for return to Earth. As part of the Perseverance payload, SuperCam is a suite of five techniques that provide critical and complementary observations via Laser-Induced Breakdown Spectroscopy (LIBS), Time-Resolved Raman and Luminescence (TRR/L), visible and near-infrared spectroscopy (VISIR), high-resolution color imaging (RMI), and acoustic recording (MIC). SuperCam operates at remote distances, primarily 2-7 m, while providing data at sub-mm to mm scales. We report on SuperCam's science objectives in the context of the Mars 2020 mission goals and ways the different techniques can address these questions. The instrument is made up of three separate subsystems: the Mast Unit is designed and built in France; the Body Unit is provided by the United States; the calibration target holder is contributed by Spain, and the targets themselves by the entire science team. This publication focuses on the design, development, and tests of the Mast Unit; companion papers describe the other units. The goal of this work is to provide an understanding of the technical choices made, the constraints that were imposed, and ultimately the validated performance of the flight model as it leaves Earth, and it will serve as the foundation for Mars operations and future processing of the data.In France was provided by the Centre National d'Etudes Spatiales (CNES). Human resources were provided in part by the Centre National de la Recherche Scientifique (CNRS) and universities. Funding was provided in the US by NASA's Mars Exploration Program. Some funding of data analyses at Los Alamos National Laboratory (LANL) was provided by laboratory-directed research and development funds

Manganese-Iron Phosphate Nodules at the Groken Site, Gale Crater, Mars

The MSL Curiosity rover investigated dark, Mn-P-enriched nodules in shallow lacustrine/fluvial sediments at the Groken site in Glen Torridon, Gale Crater, Mars. Applying all relevant information from the rover, the nodules are interpreted as pseudomorphs after original crystals of vivianite, (Fe2+,Mn2+)3(PO4)2·8H2O, that cemented the sediment soon after deposition. The nodules appear to have flat faces and linear boundaries and stand above the surrounding siltstone. ChemCam LIBS (laser-induced breakdown spectrometry) shows that the nodules have MnO abundances approximately twenty times those of the surrounding siltstone matrix, contain little CaO, and have SiO2 and Al2O3 abundances similar to those of the siltstone. A deconvolution of APXS analyses of nodule-bearing targets, interpreted here as representing the nodules’ non-silicate components, shows high concentrations of MnO, P2O5, and FeO and a molar ratio P/Mn = 2. Visible to near-infrared reflectance of the nodules (by ChemCam passive and Mastcam multispectral) is dark and relatively flat, consistent with a mixture of host siltstone, hematite, and a dark spectrally bland material (like pyrolusite, MnO2). A drill sample at the site is shown to contain minimal nodule material, implying that analyses by the CheMin and SAM instruments do not constrain the nodules’ mineralogy or composition. The fact that the nodules contain P and Mn in a small molar integer ratio, P/Mn = 2, suggests that the nodules contained a stoichiometric Mn-phosphate mineral, in which Fe did (i.e., could) not substitute for Mn. The most likely such minerals are laueite and strunzite, (Fe2+,Mn2+)3(PO4)2·8H2O and –6H2O, respectively, which occur on Earth as alteration products of other Mn-bearing phosphates including vivianite. Vivianite is a common primary and diagenetic precipitate from low-oxygen, P-enriched waters. Calculated phase equilibria show Mn-bearing vivianite could be replaced by laueite or strunzite and then by hematite plus pyrolusite as the system became more oxidizing and acidic. These data suggest that the nodules originated as vivianite, forming as euhedral crystals in the sediment, enclosing sediment grains as they grew. After formation, the nodules were oxidized—first to laueite/strunzite yielding the diagnostic P/Mn ratio, and then to hematite plus an undefined Mn oxy-hydroxide (like pyrolusite). The limited occurrence of these Mn-Fe-P nodules, both in space and time (i.e., stratigraphic position), suggests a local control on their origin. By terrestrial analogies, it is possible that the nodules precipitated near a spring or seep of Mn-rich water, generated during alteration of olivine in the underlying sediments

Rational design and characterization of alpha1-antitrypsin mutants with different polymerization propensities

0info:eu-repo/semantics/nonPublishe