No abstract

Much work has been done on algorithms for structure-based drug modeling in silico, and almost all these systems have a core need for three-dimensional geometric models. The manipulation of these models, particularly their transformation from one position to another, is a substantial computational task with design questions of its own. Solid body rotation is an important part of these transformations, and we present here a careful comparison of two established techniques: Euler angles and quaternions. The relative superiority of the quaternion method when applied to molecular docking is demonstrated by practical experiment, as is the crucial importance of proper adjustment calculations in search methods.

Advances in the capabilities of scanning transmission electron microscopes (STEMs) and electron energy loss spectrometers (EELS) over the last 2 decades have been remarkable. Modern-day monochromated, aberration corrected STEMs (MAC-STEMs) can give probe sizes of 1.1 Å at 30 kV operating voltage [1], EELS energy resolution of 4.2 meV also at 30 kV [2], and spatial resolution of ~0.3 Å through the use of 4D STEM and ptychographic reconstruction [3]. These achievements have been made possible by aberration correction, and by developments in monochromator, spectrometer and detector design. The electron-optical developments are now maturing, and further improvements in this area are likely to be more incremental. Here we summarize our work on endowing Nion electron microscopes with new capabilities via new operation modes, detectors and software.

Virtual screening is an important resource in the drug discovery community, of which protein-ligand docking is a significant part. Much software has been developed for this purpose, largely by biochemists and those in related disciplines, who pursue ever more accurate representations of molecular interactions. The resulting tools, however, are very processor-intensive. This paper describes some initial results from a project to review computational chemistry techniques for docking from a non-chemistry standpoint. An abstract blueprint for protein-ligand docking using empirical scoring functions is suggested, and this is used to discuss potential improvements. By introducing computer science tactics such as lazy function evaluation, dramatic increases to throughput can and have been realized using a real-world docking program. Naturally, they can be extended to any system that approximately corresponds to the architecture outlined.