Understanding of macrocyclic conformational landscape to reveal molecular chameleonic behavior
Title: Understanding of macrocyclic conformational landscape to reveal molecular chameleonic behavior
SNIC Project: SNIC 2021/22-244
Project Type: SNIC Small Compute
Principal Investigator: Vasanthanathan Poongavanam <vasanthanathan.poongavanam@kemi.uu.se>
Affiliation: Uppsala universitet
Duration: 2021-03-30 – 2022-04-01
Classification: 30103
Keywords:

Abstract

Drugs having a molecular weight >600-700 Da adopt a limited number of conformations in different environments. This allows them to behave as molecular chameleons that adapt to the environment, thereby combining high solubility with permeability across cell membranes and potent target binding. However, the understanding of the relationships between chemical structure, populated conformations and properties is lacking for this class of larger drugs. In this project we will investigate how the drugs partition from aqueous phase into a lipid membrane using all-atom molecular dynamics. This helps to understand conformational landscape of drugs that behave as molecular chameleons.