Synergism and Mutualism in Non-Enzymatic RNA Polymerization

The link between non-enzymatic RNA polymerization and RNA self-replication is a key step towards the “RNA world” and still far from being solved, despite extensive research. Clay minerals, lipids and, more recently, peptides were found to catalyze the non-enzymatic synthesis of RNA oligomers. Herein, a review of the main models for the formation of the first RNA polymers is presented in such a way as to emphasize the cooperation between life’s building blocks in their emergence and evolution. A logical outcome of the previous results is a combination of these models, in which RNA polymerization might have been catalyzed cooperatively by clays, lipids and peptides in one multi-component prebiotic soup. The resulting RNAs and oligopeptides might have mutualistically evolved towards functional RNAs and catalytic peptides, preceding the first RNA replication, thus supporting an RNA-peptide world. The investigation of such a system is a formidable challenge, given its complexity deriving from a tremendously large number of reactants and innumerable products. A rudimentary experimental design is outlined, which could be used in an initial attempt to study a quaternary component system

A Computational Study of Mg 2+ Dehydration in Aqueous Solution in the Presence of HS- and Other Monovalent Anions-Insights to Dolomite Formation

Massive sedimentary dolomite formed at near-Earth’s surface temperatures is abundant in the ancient geological rock record compared to modern deposition. Extensive experimental work to synthesize dolomite at low temperature and to reveal the formation mechanism has been attempted previously. Sulfide, the product of bacterial sulfate reduction, has been proposed in the literature to play an active role in promoting dolomite formation by facilitating desolvation of Mg2+ in the bulk solution and, thus, incorporation into the dolomite crystal structure. Chemical intuition, however, does not suggest any particular characteristic of HS− that would render it an efficient promoter of Mg2+ desolvation in solution. In order to examine the previously proposed hypothesis, we conduct an ab initio reaction path ensemble (RPE) study along a dissociative mechanism to determine the energy penalty of removing a first-shell water molecule around Mg2+ compared to Mg2+ with HS− located in the second coordination shell. The solvent effect and specific hydrogen-bond interactions from water beyond the first-solvation shell are addressed using large cluster models, where up to the second layer of Mg2+ hydration and the first solvation-shell of HS− are included. Within the context our modeling approach, we find that HS− has little, if any, effect on lowering the Mg2+ dehydration barrier in aqueous solution. Alternative mechanisms must then be invoked to explain the apparent promotional effect of HS− on Mg2+ dehydration kinetics

Structure analysis of collagen fibril at atomic-level resolution and its implications for intra-fibrillar transport in bone biomineralization

Bone is a hierarchical biocomposite material in which a collagen fibril matrix self-assembled in a three-dimensional (3-D) pseudohexagonal array controls many important processes in mineralization such as providing the pathways by which calcium and phosphate species are delivered and a template for the earliest nucleation sites, determining the spatial distribution of the mineral and the topology for binding of associated non-collagenous proteins. However, the structural characteristics of collagen molecules in the fibril remain unclear at the atomic level. Here we performed the first large-scale molecular dynamics simulations to provide a comprehensive all-atom structural analysis of the entire fibril of Type I collagen including intra-fibrillar water distribution. We found that the ideal fibril structure is preserved in specific sites where the earliest nucleation occurs, but is severely distorted in areas that mineralize later. In detail, the ideal pseudohexagonal structure is well-preserved in the overlap zone (c1, c2 and b bands), in the a bands of the hole zone but is severely distorted at the hole/overlap transition (d and c3 bands). As a result, the expected uniform channel,\u27\u27 formed by connecting holes in adjacent unit cells along the b-axis, and having dimensions of 1.5 nm height along the a-axis and width of 40 nm along the c-axis is not formed. The expected uniform channel of 1.5 nm height is preserved only in the a bands in a narrow sub-channel region only 5.8 nm wide. At the hole/overlap transition, an irregular, tortuous sub-channel of widely varying dimensions (similar to 1.8-4.0 nm height x similar to 3.0 nm width) is formed. The well-defined sub-channel in the a bands along with their preferred orientation of charged amino acid residues could facilitate faster molecular diffusion than the tortuous sub-channels and ionic interactions, thus providing the first nucleation sites. Intra-fibrillar water occupies nano-spaces and shows low density (similar to 0.7 g cm(-3)), which should promote dehydration of ion species. These results provide the first atomic-level understanding of the structure of the collagen fibril and the properties of the aqueous compartments within the fibril, which offer a physical, chemical and steric explanation for calcium phosphate infiltration paths and for the initiation of mineralization at the a band collagen fibril. The mechanism revealed here for the observed specificity of collagen biomineralization in bone formation ultimately contributes to the biochemical and biomechanical functions of the skeleton

Biomimetic and Nanostructured Hybrid Bioactive Glass

Inspired by nature\u27s toughening mechanisms, we designed a new polyhedral oligomeric silsesquioxane (POSS)-derived hybrid glass (PHG) that has covalent interactions on the molecular scale between the inorganic POSS cage and organic phase. These features allow “elastic deformation” of the inorganic POSS cage in limited scale. The final product is a bulk hybrid material with toughness (3.56 ± 0.25 MPa·m1/2) similar to natural bone (2.4–5.3 MPa·m1/2). PHG exhibited excellent bioactivity by promoting the formation of plate-like hydroxyapatite on its surface in simulated body fluid and showed good cell adhesion. PHG also can be a platform to guide adipose tissue-derived mesenchymal stem cells differentiation and mineralization. The key structural features of this material can be used to guide the design of bio-inspired composites with unique toughness, which would be of great benefit to hard tissue engineering