Ligand GA: a genetic algorithm for automated protein inhibitor design

Ligand GA is introduced in this work and approaches the problem of finding small molecules inhibiting protein functions by using the protein site to find close to optimal or optimal small molecule binders. Genetic algorithms (GA) are an effective means for approximating or solving computationally hard mathematics problems with large search spaces such as this one. The algorithm is designed to include constraints on the generated molecules from ADME restriction, localization in a binding site, specified hydrogen bond requirements, toxicity prevention from multiple proteins, sub-structure restrictions, and database inclusion. This algorithm and work is in the context of computational modeling, ligand design and docking to protein sites.

Phosphorescent Organometallic Knots of Gold(I)-Bis(acetylide) Strands Directed by Copper(I) π-Coordination

Through elaborate ligand design to create knotted structures with specific topologies is a major challenge for chemists. In this work, the self-assembly between U-shape 3,6-di-tert-butyl-1,8-diethynyl-9H-carbazole (H2L) and Au+ through gold(I)-bis(acetylide) linkages under π-bonded Cu+ template gives rise to complex 1 with two interlocked metallostrands as well as complexes 3 (n = 3) and 4 (n = 4) with [(AuL)n]n- metallostrands showing trefoil knot topology. Upon incorporating two [Au(dppb)Au]2+ (dppb = Ph2P(CH2)4PPh2) moieties through bis(Au-acetylide) coordination bonds, the interlocked structure (1) is fully closed to form a figure-eight knotted structure in complex 2. The folding and threading of metallocyclic strings are directed by Cu+, which are π-ligated to two or three acetylides to generate double-folding or triple-folding cross points. Complexes 1-4 show intense phosphorescence in both solutions and solid states at ambient temperature, originating from admixture of metal centered 3[d®p/s], 3IL (intraligand), and 3[p (L) ® s/p (Au/Cu)] 3LMCT triplet states.