Kinetic barriers in the isomerization of substituted ureas: implications for computer-aided drug design.

ABSTRACT: Urea derivatives are ubiquitously found in many chemical disciplines. N,N'-substituted ureas may show different conformational preferences depending on their substitution pattern. The high energetic barrier for isomerization of the cis and trans state poses additional challenges on computational simulation techniques aiming at a reproduction of the biological properties of urea derivatives. Herein, we investigate energetics of urea conformations and their interconversion using a broad spectrum of methodologies ranging from data mining, via quantum chemistry to molecular dynamics simulation and free energy calculations. We find that the inversion of urea conformations is inherently slow and beyond the time scale of typical simulation protocols. Therefore, extra care needs to be taken by com

SUBMITTER: Loeffler JR 

PROVIDER: S-EPMC4912590 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature