Energy landscapes and persistent minima.

We consider a coarse-graining of high-dimensional potential energy landscapes based upon persistences, which correspond to lowest barrier heights to lower-energy minima. Persistences can be calculated efficiently for local minima in kinetic transition networks that are based on stationary points of the prevailing energy landscape. The networks studied here represent peptides, proteins, nucleic acids, an atomic cluster, and a glassy system. Minima with high persistence values are likely to represent some form of alternative structural morphology, which, if appreciably populated at the prevailing temperature, could compete with the global minimum (defined as infinitely persistent). Threshold values on persistences (and in some cases equilibrium occupation probabilities) have therefore been used in this work to select subsets of minima, which were then analysed to see how well they can represent features of the full network. Simplified disconnectivity graphs showing only the selected minima can convey the funnelling (including any multiple-funnel) characteristics of the corresponding full graphs. The effect of the choice of persistence threshold on the reduced disconnectivity graphs was considered for a system with a hierarchical, glassy landscape. Sets of persistent minima were also found to be useful in comparing networks for the same system sampled under different conditions, using minimum oriented spanning forests.D.J.W and J.M.C gratefully acknowledge funding from the European Research Council [267369].This is the author accepted manuscript. The final version is available at http://scitation.aip.org/content/aip/journal/jcp/144/5/10.1063/1.4941052

Ancient horizontal gene transfer and the last common ancestors

Background The genomic history of prokaryotic organismal lineages is marked by extensive horizontal gene transfer (HGT) between groups of organisms at all taxonomic levels. These HGT events have played an essential role in the origin and distribution of biological innovations. Analyses of ancient gene families show that HGT existed in the distant past, even at the time of the organismal last universal common ancestor (LUCA). Most gene transfers originated in lineages that have since gone extinct. Therefore, one cannot assume that the last common ancestors of each gene were all present in the same cell representing the cellular ancestor of all extant life. Results Organisms existing as part of a diverse ecosystem at the time of LUCA likely shared genetic material between lineages. If these other lineages persisted for some time, HGT with the descendants of LUCA could have continued into the bacterial and archaeal lineages. Phylogenetic analyses of aminoacyl-tRNA synthetase protein families support the hypothesis that the molecular common ancestors of the most ancient gene families did not all coincide in space and time. This is most apparent in the evolutionary histories of seryl-tRNA synthetase and threonyl-tRNA synthetase protein families, each containing highly divergent “rare” forms, as well as the sparse phylogenetic distributions of pyrrolysyl-tRNA synthetase, and the bacterial heterodimeric form of glycyl-tRNA synthetase. These topologies and phyletic distributions are consistent with horizontal transfers from ancient, likely extinct branches of the tree of life. Conclusions Of all the organisms that may have existed at the time of LUCA, by definition only one lineage is survived by known progeny; however, this lineage retains a genomic record of heterogeneous genetic origins. The evolutionary histories of aminoacyl-tRNA synthetases (aaRS) are especially informative in detecting this signal, as they perform primordial biological functions, have undergone several ancient HGT events, and contain many sites with low substitution rates allowing deep phylogenetic reconstruction. We conclude that some aaRS families contain groups that diverge before LUCA. We propose that these ancient gene variants be described by the term “hypnologs”, reflecting their ancient, reticulate origin from a time in life history that has been all but erased”.National Science Foundation (U.S.) (Grant DEB 0830024)Exobiology Program (U.S.) (Grant NNX10AR85G)United States. National Aeronautics and Space Administration (Postdoctoral Program

Synthesis, Identification, and Structure Elucidation of Adducts Formed by Reactions of Hydroxycinnamic Acids with Glutathione or Cysteinylglycine

Grape polyphenols, especially hydroxycinnamic acids such as caftaric and caffeic acid, are prone to enzymatic oxidation reactions during the winemaking process, forming <i>o</i>-quinones and leading to color darkening. Glutathione is capable of trapping these <i>o</i>-quinones and thus limiting juice browning. In this study, the addition of glutathione or cysteinylglycine onto caftaric or caffeic acid <i>o</i>-quinones formed by polyphenoloxidase-catalyzed reactions was investigated by UPLC-DAD-ESIMS and NMR data analyses. Complete identification of adducts has been achieved via NMR data. The results confirmed that the favored reaction is the substitution of the sulfanyl group of cysteine at C-2 of the aromatic ring. Several minor isomers, namely, the <i>cis</i>-isomer of the 2-<i>S</i> adduct and <i>trans</i>-isomers of the 5-<i>S</i> and 6-<i>S</i> adducts, and the 2,5-di-<i>S</i>-glutathionyl adducts were also identified and quantified by qNMR. With the exception of 2-(<i>S</i>-glutathionyl)- and 2,5-di­(<i>S</i>-glutathionyl)-<i>trans</i>-caftaric acid, these products had never been formally identified. In particular, the 5-<i>S</i> and 6-<i>S</i> derivatives are reported here for the first time. The first formal identification of 2-<i>S cis</i>-derivatives is also provided. Moreover, NMR and UPLC-DAD-ESIMS analysis showed that signature UV and MS spectra can serve as markers of the conformation and substitution position in the aromatic ring for each of the isomers

Research data supporting "Energy Landscapes and Persistent Minima"

Kinetic transition networks (databases of connected stationary points on the potential energy surface) for dialanine and tetraalanine peptides, the 38-atom Lennard-Jones cluster, a 60-atom binary Lennard-Jones mixture, a 69-bead model protein, binding modes for influenza virus, and a UUCG RNA tetraloop. These networks, obtained in previous work, are analysed here using topological persistence, to obtain subsets of local minima and hence a reduced description of the underlying energy landscape.This work was supported by the ERC [grant number 267369]