Crystallization phasing and obtaining high-quality crystals are bottleneck challenges for the X-ray crystallographic analysis of nucleic acids, especially when dynamic behavior is to be inferred from crystallographic B-factors. Crystallization of DNA duplexes, normally existing in the B-form in solution, is especially challenging, as the high salt used in many crystallization processes favors their transformation to A-form DNA duplexes. To address crystallization challenges while avoiding structural perturbation, we explored atom-specific incorporation to place a selenium atom on the 2'-β (arabino) position of the 2'-deoxyribose ring. This incorporation is expected to favor the B-form of a DNA duplex during crystallization. Here, we report the first synthesis of the β-2'-MeSe-thymidine (^SeT) nucleoside, the corresponding Se-phosphoramidite, and Se-containing DNA oligonucleotides. We found that particular Se-DNAs form crystals that are surprisingly larger than we have often observed, having higher quality and giving improved diffraction resolution when compared to crystals from analogous standard oligonucleotides. Surprisingly, one duplex made from a self-complementary Se-containing oligonucleotide gave crystals 600 × 200 µm² in size; this is 10–100 times larger in volume than the corresponding crystals grown from native DNA. CD and a solved crystal structure showed that the selenium in the β-orientation did not perturb the native structure and gave diffraction data from which dynamic information could be extracted. Crystals of this size are especially important for neutron diffraction studies. Moreover, we discovered that the high-quality Se-DNA crystals diffracted to 1.15 Å. The Se-derivatized structure was virtually identical with the native structure. These discoveries suggest a simple strategy to address other crystallization challenges in nucleic acid crystallography, a strategy whose scope deserves further exploration.

Given the importance of catalysts in the chemical industry, they have been extensively investigated by experimental and numerical methods. With the development of computational algorithms and computer hardware, large-scale simulations have enabled influential studies with more atomic details reflecting microscopic mechanisms. This review provides a comprehensive summary of recent developments in molecular dynamics, including ab initio molecular dynamics and reaction force-field molecular dynamics. Recent research on both approaches to catalyst calculations is reviewed, including growth, dehydrogenation, hydrogenation, oxidation reactions, bias, and recombination of carbon materials that can guide catalyst calculations. Machine learning has attracted increasing interest in recent years, and its combination with the field of catalysts has inspired promising development approaches. Its applications in machine learning potential, catalyst design, performance prediction, structure optimization, and classification have been summarized in detail. This review hopes to shed light and perspective on ML approaches in catalysts.

Selenium atom-specific functionalization can offer nucleic acids with many unique and novel properties (such as facilitated crystallization and phase determination) without significant perturbation of 3D structures of nucleic acids and their protein complexes. Nucleic acids possess not only the ability to store genetic information and participate in transcription and translation, but also the capacity to adopt well-defined 3D structures, which can be readily adjusted to meet various functional needs (such as catalysis and therapeutics). Although the importance of numerous nucleic acids in catalysis, gene expression, protein binding and therapeutics has been acknowledged by the entire scientific society, current understanding of nucleic acid-protein functions and structures is still limited, especially highresolution structures. This novel Se-atom-specific functionalization will provide important tools to investigate nucleic acid structure/folding, recognition and catalysis, to study nucleic acids and their protein interactions, to improve biochemical and biophysical properties of nucleic acids, and to explore potential nucleic acid therapeutics and diagnostics. Our presentation will focus on the most recent selenium-atom functionalization of nucleic acids and their potential applications in 3D structure-and-function studies and anticancer therapeutics in molecular medicine.