Molecular dynamics simulations of human [Formula: see text]: the role of modified bases in mRNA recognition

Accuracy in translation of the genetic code into proteins depends upon correct tRNA–mRNA recognition in the context of the ribosome. In human [Formula: see text] three modified bases are present in the anticodon stem–loop—2-methylthio-N6-threonylcarbamoyladenosine at position 37 (ms(2)t(6)A37), 5-methoxycarbonylmethyl-2-thiouridine at position 34 (mcm(5)s(2)U34) and pseudouridine (ψ) at position 39—two of which, ms(2)t(6)A37 and mcm(5)s(2)U34, are required to achieve wild-type binding activity of wild-type human [Formula: see text] [C. Yarian, M. Marszalek, E. Sochacka, A. Malkiewicz, R. Guenther, A. Miskiewicz and P. F. Agris (2000) Biochemistry, 39, 13390–13395]. Molecular dynamics simulations of nine tRNA anticodon stem–loops with different combinations of nonstandard bases were performed. The wild-type simulation exhibited a canonical anticodon stair-stepped conformation. The ms(2)t(6) modification at position 37 is required for maintenance of this structure and reduces solvent accessibility of U36. Ms(2)t(6)A37 generally hydrogen bonds across the loop and may prevent U36 from rotating into solution. A water molecule does coordinate to ψ39 most of the simulation time but weakly, as most of the residence lifetimes are <40 ps

Backbone–Base Interactions Critical to Quantum Stabilization of Transfer RNA Anticodon Structure

Transfer RNA (tRNA) anticodons adopt a highly ordered 3′-stack without significant base overlap. Density functional theory at the M06-2X/6-31+G­(d,p) level in combination with natural bond orbital analysis was utilized to calculate the intramolecular interactions within the tRNA anticodon that are responsible for stabilizing the stair-stepped conformation. Ten tRNA X-ray crystal structures were obtained from the PDB databank and were trimmed to include only the anticodon bases. Hydrogenic positions were added and optimized for the structures in the stair-stepped conformation. The sugar–phosphate backbone has been retained for these calculations, revealing the role it plays in RNA structural stability. It was found that electrostatic interactions between the sugar–phosphate backbone and the base provide the most stability, rather than the traditionally studied interbase stacking. Base-stacking interactions, though present, were weak and inconsistent. Aqueous solvation was found to have little effect on the intramolecular interactions

The Impacts of the Molecular Education and Research Consortium in Undergraduate Computational Chemistry on the Careers of Women in Computational Chemistry

The Molecular Education and Research Consortium in Undergraduate Computational Chemistry (MERCURY) has supported a diverse group of faculty and students for over 20 years by providing computational resources as well as networking opportunities and professional support. The consortium comprises 38 faculty (42% women) at 34 different institutions, who have trained nearly 900 undergraduate students, more than two-thirds of whom identify as women and one-quarter identify as students of color. MERCURY provides a model for the support necessary for faculty to achieve professional advancement and career satisfaction. The range of experiences and expertise of the consortium members provides excellent networking opportunities that allow MERCURY faculty to support each other’s teaching, research, and service needs, including generating meaningful scientific advancements and outcomes with undergraduate researchers as well as being leaders at the departmental, institutional, and national levels. While all MERCURY faculty benefit from these supports, the disproportionate number of women in the consortium, relative to their representation in computational sciences generally, produces a sizable impact on advancing women in the computational sciences. In this report, the women of MERCURY share how the consortium has benefited their careers and the careers of their students

AmberTools

AmberTools is a free and open-source collection of programs used to set up, run, and analyze molecular simulations. The newer features contained within AmberTools23 are briefly described in this Application note