Peptidic Macrocycles - Conformational Sampling and Thermodynamic Characterization.

ABSTRACT: Macrocycles are of considerable interest as highly specific drug candidates, yet they challenge standard conformer generators with their large number of rotatable bonds and conformational restrictions. Here, we present a molecular dynamics-based routine that bypasses current limitations in conformational sampling and extensively profiles the free energy landscape of peptidic macrocycles in solution. We perform accelerated molecular dynamics simulations to capture a diverse conformational ensemble. By applying an energetic cutoff, followed by geometric clustering, we demonstrate the striking robustness and efficiency of the approach in identifying highly populated conformational states of cyclic peptides. The resulting structural and thermodynamic information is benchmarked against interpro

SUBMITTER: Kamenik AS 

PROVIDER: S-EPMC5974701 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature