Formation of the Codon Degeneracy during Interdependent Development between Metabolism and Replication

Nirenberg’s genetic code chart shows a profound correspondence between codons and amino acids. The aim of this article is to try to explain the primordial formation of the codon degeneracy. It remains a puzzle how informative molecules arose from the supposed prebiotic random sequences. If introducing an initial driving force based on the relative stabilities of triplex base pairs, the prebiotic sequence evolution became innately nonrandom. Thus, the primordial assignment of the 64 codons to the 20 amino acids has been explained in detail according to base substitutions during the coevolution of tRNAs with aaRSs; meanwhile, the classification of aaRSs has also been explained.

MELD-accelerated molecular dynamics help determine amyloid fibril structures

It is challenging to determine the structures of protein fibrils such as amyloids. In principle, Molecular Dynamics (MD) modeling can aid experiments, but normal MD has been impractical for these large multi-molecules. Here, we show that MELD accelerated MD (MELD x MD) can give amyloid structures from limited data. Five long-chain fibril structures are accurately predicted from NMR and Solid State NMR (SSNMR) data. Ten short-chain fibril structures are accurately predicted from more limited restraints information derived from the knowledge of strand directions. Although the present study only tests against structure predictions – which are the most detailed form of validation currently available – the main promise of this physical approach is ultimately in going beyond structures to also give mechanical properties, conformational ensembles, and relative stabilities.

Gold-Catalyzed Complementary Nitroalkyne Internal Redox Process: A DFT Study

Gold-catalysis, in this century, is one of the most emerging and promising new areas of research in organic synthesis. During the last two decades, a wide range of distinct synthetic methodologies have been unveiled employing homogeneous gold catalysis and aptly applied in the synthesis of numerous natural products and biologically active molecules. Among these, the reactions involving α-oxo gold carbene/α-imino gold carbene intermediates are of contemporary interest, in view of their synthetic potential and also due to the need to understand the bonding involved in these complexes. In this manuscript, we document the theoretical investigations on the regio-selectivity dependence of substitution on the gold-catalyzed cycloisomerization of o-nitroarylalkyne derivatives. We have also studied the relative stabilities of α-oxo gold carbene intermediates.

Native mass spectrometry analyses of chaperonin complex TRiC/CCT reveal subunit N-terminal processing and re-association patterns

The eukaryotic chaperonin TRiC/CCT is a large ATP-dependent complex essential for cellular protein folding. Its subunit arrangement into two stacked eight-membered hetero-oligomeric rings is conserved from yeast to man. A recent breakthrough enables production of functional human TRiC (hTRiC) from insect cells. Here, we apply a suite of mass spectrometry techniques to characterize recombinant hTRiC. We find all subunits CCT1-8 are N-terminally processed by combinations of methionine excision and acetylation observed in native human TRiC. Dissociation by organic solvents yields primarily monomeric subunits with a small population of CCT dimers. Notably, some dimers feature non-canonical inter-subunit contacts absent in the initial hTRiC. This indicates individual CCT monomers can promiscuously re-assemble into dimers, and lack the information to assume the specific interface pairings in the holocomplex. CCT5 is consistently the most stable subunit and engages in the greatest number of non-canonical dimer pairings. These findings confirm physiologically relevant post-translational processing and function of recombinant hTRiC and offer quantitative insight into the relative stabilities of TRiC subunits and interfaces, a key step toward reconstructing its assembly mechanism. Our results also highlight the importance of assigning contacts identified by native mass spectrometry after solution dissociation as canonical or non-canonical when investigating multimeric assemblies.

Deep learning the structural determinants of protein biochemical properties by comparing structural ensembles with DiffNets

Understanding the structural determinants of a protein’s biochemical properties, such as activity and stability, is a major challenge in biology and medicine. Comparing computer simulations of protein variants with different biochemical properties is an increasingly powerful means to drive progress. However, success often hinges on dimensionality reduction algorithms for simplifying the complex ensemble of structures each variant adopts. Unfortunately, common algorithms rely on potentially misleading assumptions about what structural features are important, such as emphasizing larger geometric changes over smaller ones. Here we present DiffNets, self-supervised autoencoders that avoid such assumptions, and automatically identify the relevant features, by requiring that the low-dimensional representations they learn are sufficient to predict the biochemical differences between protein variants. For example, DiffNets automatically identify subtle structural signatures that predict the relative stabilities of β-lactamase variants and duty ratios of myosin isoforms. DiffNets should also be applicable to understanding other perturbations, such as ligand binding.

Correcting Frost Diagram Misconceptions Using Interactive Frost Diagrams

<p>Frost diagrams provide convenient illustrations of the aqueous reduction potentials and thermodynamic tendencies of different oxidation states of an element. Undergraduate textbooks often describe the lowest point on a Frost diagram as the most stable oxidation state of the element, but this interpretation is incorrect because the thermodynamic stability of each oxidation state depends on the specific redox conditions in solution (i.e., the potential applied by the environment or an electrode). Further confusion is caused by the widespread use of different, contradictory conventions for labeling the y-axis of these diagrams as either n<i>E</i>° or −n<i>E</i>°, among other possibilities. To aid in discussing and correcting these common mistakes, we introduce a series of interactive Frost diagrams that illustrate the conditional dependence of the relative stabilities of each oxidation state of an element. We include instructor’s notes for using these interactive diagrams and a written activity for students to complete using these diagrams.</p>

Correcting Frost Diagram Misconceptions Using Interactive Frost Diagrams

<p>Frost diagrams provide convenient illustrations of the aqueous reduction potentials and thermodynamic tendencies of different oxidation states of an element. Undergraduate textbooks often describe the lowest point on a Frost diagram as the most stable oxidation state of the element, but this interpretation is incorrect because the thermodynamic stability of each oxidation state depends on the specific redox conditions in solution (i.e., the potential applied by the environment or an electrode). Further confusion is caused by the widespread use of different, contradictory conventions for labeling the y-axis of these diagrams as either n<i>E</i>° or −n<i>E</i>°, among other possibilities. To aid in discussing and correcting these common mistakes, we introduce a series of interactive Frost diagrams that illustrate the conditional dependence of the relative stabilities of each oxidation state of an element. We include instructor’s notes for using these interactive diagrams and a written activity for students to complete using these diagrams.</p>