Computational chemistry is a branch of chemistry that uses the results of theoretical chemistry incorporated into efficient computer programs to calculate the structures and properties of molecules and solids, applying these programs to real chemical problems.We use a variety of software packages i.e. Amber, Orca, DFT to perform our calculations to the best precision.
Molecular simulations are an important research tool used to explore and provide insights to a variety of phenomena in molecular systems. There has been a seldom application of these tools in High Performance liquid chromatography. Whilst the preferred techniques for method development in HPLC have been successful, they solely depend on guides proposed in different texts which in turn have limitations and consume a considerable amount of time as they are based on a trial and error approach. In this work we will utilize the molecular modelling principle tools from molecular dynamics to consider molecular simulations as an alternative approach towards method development in reversed phase-high performance chromatography. The analysis obtained from the molecular simulations is examined to extract information on the mobile phase-analyte interactions, effects of ions on those interactions and the effects of change in mobile phase composition on the interaction. The results of the analysis will shine a light on the significance of molecular simulations in method development and its possible application in mobile phase modelling.
The development of peptide stapling techniques to stabilise α-helical secondary structure motifs of peptides led to the design of modulators of protein–protein interactions, which had been considered undruggable for a long time. We disclose a novel approach towards peptide stapling utilising macrocyclisation by late-stage Suzuki–Miyaura cross-coupling of bromotryptophan-containing peptides of the catenin-binding domain of axin. Optimisation of the linker length in order to find a compromise between both sufficient linker rigidity and flexibility resulted in a peptide with an increased α-helicity and enhanced binding affinity to its native binding partner β-catenin. An increased proteolytic stability against proteinase K has been demonstrated. In this paper, the identification of two isomers of P5 by LC–MS led us investigate the possibility of diastereomers and conformers in the macrocycle.