Protein dynamics and function
Proteins function through fluctuating ensembles rather than a single static structure. Motions across multiple time and length scales reorganize the molecular interactions that govern catalysis, ion permeation, ligand recognition, and allostery. Understanding these coupled structural and electrostatic fluctuations is essential for connecting atomistic dynamics to experimentally observed function.
The Welborn group combines molecular dynamics, polarizable force fields, free-energy calculations, and electric-field analysis to identify the interactions that control protein behavior. Our recent work examines preorganized electric fields that guide sodium ions through voltage-gated channels, the dynamic determinants of protein–ligand binding, and molecular strategies for mitigating product inhibition in enzymes.
Electric fields provide a common language for connecting protein structure, dynamics, and function. Charged residues, molecular dipoles, solvent molecules, and bound ligands collectively generate fields that respond to conformational motion and can promote or oppose molecular events. By quantifying these fields and their correlations across a protein, we uncover residues and dynamical pathways that regulate catalysis, transport, reactivity, binding, and allostery. Our goal is to translate these mechanistic insights into principles for protein engineering, inhibitor design, and the prediction of biological function from molecular simulation.