Conformational Sampling Deciphers the Chameleonic Properties of a VHL-Based Degrader.

ABSTRACT: Chameleonicity (the capacity of a molecule to adapt its conformations to the environment) may help to identify orally bioavailable drugs in the beyond-Rule-of-5 chemical space. Computational methods to predict the chameleonic behaviour of degraders have not yet been reported and the identification of molecular chameleons still relies on experimental evidence. Therefore, there is a need to tune predictions with experimental data. Here, we employ PROTAC-1 (a passively cell-permeable degrader), for which NMR and physicochemical data prove the chameleonic behaviour, to benchmark the capacity of two conformational sampling algorithms and selection schemes. To characterize the conformational ensembles in both polar and nonpolar environments, we compute three molecular properties proven to be ess

SUBMITTER: Ermondi G 

PROVIDER: S-EPMC9861353 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature