Conformational Flexibility of Organic Molecules in Solution

(148 Words, 1 Minutes)

Understanding the conformational confiuguration of organic molecules in solution is integral to understanding their behaviour and function, encompassing a variety of phenomena including biomolecular aggregation, MOF synthesis, the nucleation of organic molecules and the dynamics of molecular machines. We harness the power of unsupervised clustering to untangle the conformational complexity of highly flexible drug molecules. Using data generated from enhanced sampling molecular dynamics simulations, the endless number of contortions undertaken by a molecule in solution can be refined into a set of key conformers. The relative population of these conformers evolve as the system moves from the solution to the crystal phase, allowing us to trace the path taken by the molecule as it settles into its position in the lattice.

Relevant Publications:

• Into the dynamics of rotaxanes at atomistic resolution. L Leanza, C Perego, L Pesce, M Salvalaglio, M von Delius, GM Pavan Chemical Science 14 (24), 6716-6729, 2023.
• Polymorph-Selective Role of Hydrogen Bonding and π–π Stacking in p-Aminobenzoic Acid Solutions, R Bobrovs, L Drunka, AA Auzins, K Jaudzems, M Salvalaglio, Crystal Growth & Design 21 (1), 436-448, 2020.
• Molecular level understanding of the free energy landscape in early stages of metal–organic framework nucleation L Kollias, DC Cantu, MA Tubbs, R Rousseau, VA Glezakou, M Salvalaglio Journal of the American Chemical Society 141 (14), 6073-6081, 2019.
• Modeling the Structure and Interactions of Intrinsically Disordered Peptides with Multiple Replica, Metadynamics-Based Sampling Methods and Force-Field Combinations. L Li, T Casalini, P Arosio, M Salvalaglio. Journal of Chemical Theory and Computation, 2022.
• Dynamics and thermodynamics of Ibuprofen conformational isomerism at the crystal/solution interface, V Marinova, GPF Wood, I Marziano, M Salvalaglio, Journal of chemical theory and computation 14 (12), 6484-6494, 2018.
• Identifying conformational isomers of organic molecules in solution via unsupervised clustering. V Marinova, L Dodd, SJ Lee, GPF Wood, I Marziano, M Salvalaglio, Journal of Chemical Information and Modeling 61 (5), 2263-2273, 2021.