Exhaustive Conformational Sampling of Complex Fused Ring Macrocycles Using Inverse Kinematics.

ABSTRACT: Natural product and synthetic macrocycles are chemically and topologically diverse. An efficient, accurate, and general method for generating macrocycle conformations would enable structure-based design of macrocycle drugs or host-guest complexes. Computational sampling also provides insight into transiently populated states, complementing crystallographic and NMR data. Here, we report a new algorithm, BRIKARD, that addresses this challenge through computational algebraic geometry and inverse kinematics together with local energy minimization. BRIKARD is demonstrated on 67 diverse macrocycles with structural data, encompassing various ring topologies. We find this approach enumerates diverse structures with macrocyclic RMSD < 1.0 Å to the experimental conformation for 85% of our data set i

SUBMITTER: Coutsias EA 

PROVIDER: S-EPMC5465426 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature