Systemic Evolutionary Chemical Space Exploration For Drug Discovery

Chemical space exploration is a major task of the hit-finding process during the pursuit of novel chemical entities. Compared with other screening technologies, computational de novo design has become a popular approach to overcome the limitation of current chemical libraries. Here, we reported a de novo design platform named systemic evolutionary chemical space explorer (SECSE). The platform was conceptually inspired by fragment-based drug design, that miniaturized a “lego-building” process within the pocket of a certain target. The key of virtual hits generation was then turned into a computational search problem. To enhance search and optimization, human intelligence and deep learning were integrated. Application of SECSE against PHGDH, proved its potential in finding novel and diverse small molecules that are attractive starting points for further validation. This platform is open-sourced and the code is available at http://github.com/KeenThera/SECSE.

Textual Indigence in the Archive

Beginning with a profile of encyclopedic aspirations in Don DeLillo’s novel Underworld, this chapter extends the analysis through Moby-Dick by Herman Melville and The Magic Mountain by Thomas Mann. These are among numerous instances of cultural and intellectual audacity characterized as the encyclopedic novel after the publication of Gravity’s Rainbow by Thomas Pynchon. The analysis expands by recounting the history of the encyclopedia as a form emerging from the earlier genre of the anatomy. This legacy, pioneering the cross-referencing system familiar from reference works in general, is now thoroughly integrated into our computational search engines. The novels characterized as encyclopedic, however, turn out to resist the sense of instantaneity and rapidity evident in digital platforms, going so far as to find value in indigence, revealed as the art of non-compliance with compulsory forms of “progress.”