A. Sofia F. Oliveira
University of Bristol, Bristol, BS81TS, UK
Email: sofia.oliveira@bristol.ac.uk
Abstract.
Proteins are neither static entities nor work in isolation under physiological conditions. In fact, it is the opposite; their function is closely linked to their ability to adopt and transition between multiple conformational states, with even subtle environmental changes capable of shifting the equilibrium among these states. Understanding this intricate dynamics and the complex interplay between protein structure and function is fundamental to biology, with this ongoing pursuit driving the development of advanced biomolecular simulation techniques.
Here, we highlight the dynamical nonequilibrium molecular dynamics (D-NEMD) method [1-2], a cutting-edge approach that offers unique insights into biomolecular behaviour. In particular, D-NEMD allows us to explore how structural changes propagate through a protein and how distant regions communicate (a phenomenon known as allostery). By combining simulations in equilibrium and nonequilibrium conditions, D-NEMD captures the evolution of a protein’s response to external triggers, revealing unique mechanistic details that are often inaccessible through equilibrium methods. We will introduce the essential features of D-NEMD and demonstrate its versatility through applications to a range of biological systems, from soluble proteins to integral membrane complexes. Case studies include enzymes involved in antibiotic resistance, viral proteins, and receptors implicated in addiction and cancer [1-2]. Across these diverse systems, D-NEMD has proven to be a powerful tool for mapping structural responses, revealing hidden communication pathways, and identifying structural determinants of function. This knowledge not only deepens our molecular-level understanding of biological processes but also offers practical insights for experimental design and drug discovery.
References:
- Oliveira et al. Eur Phys J B, 2021, 94, 144
- Balega et al. Mol Phys, 2024, 123, e2428350