Machine learning approaches to optimize small-molecule inhibitors for RNA targeting.

In the era of data science, data-driven algorithms have emerged as powerful platforms that can consolidate bioisosteric rules for preferential modifications on small molecules with a common molecular scaffold. Here we present complementary data-driven algorithms to minimize the search in chemical space for phenylthiazole-containing molecules that bind the RNA hairpin within the ribosomal peptidyl transferase center (PTC) of Mycobacterium tuberculosis. Our results indicate visual, geometrical, and chemical features that enhance the binding to the targeted RNA. Functional validation was conducted after synthesizing 10 small molecules pinpointed computationally. Four of the 10 were found to be potent inhibitors that target hairpin 91 in the ribosomal PTC of M. tuberculosis and, as a result, stop translation.

Full control of the spectral polarization of ultrashort pulses.

The spectral polarization of an ultrashort pulse is fully controlled by a novel pulse shaper design, including three liquid-crystal spatial light modulator arrays at three different orientations. The added degree of controllability permits generation of previously unattainable pulse shapes, with possible applications in multidimensional spectroscopy, coherent control, and ultrafast polarization gating.