Non-equilibrium simulations: a dream approach for studying structural changes in proteins?

Sofia Oliveira, BBSRC Discovery Fellow, University of Bristol, UK

Host: Rita Sobral, UCIBIO, NOVA

ZOOM link: https://ucibio.pt/l/GuestSeminars

Abstract:

Proteins are neither static nor work in isolation in physiological conditions. In fact, it is the opposite; proteins are continuously moving and switching between many different conformations. Changes in the environment can shift the balance between this multitude of conformations, ultimately determining the protein's macroscopic behaviour. The binding of ions and small ligands and peptides, changes in voltage, pH, and temperature and light absorption by light-harvesting complexes are all good examples of external perturbations that can induce changes in protein structure and dynamics, thus affecting their function. 

Even though it is possible to experimentally determine the positions of the atoms in a protein (e.g. using cryo-EM or X-ray crystallography), in some cases, the effects of making changes to the protein (e.g. mutations or the binding of ligands and ions) are not obvious. An alternative to experimental approaches is the application of computer simulations.
Several computational approaches have been developed over the years to study conformational changes in proteins in silico and understand how these changes shape function. Here, we will focus on an emerging approach named dynamical non-equilibrium molecular dynamics (D-NEMD) simulations, which combines simulations in stationary (in particular, equilibrium) and non-equilibrium conditions. This approach, which was initially proposed in the seventies by Ciccotti et al., is undergoing a renaissance and having increasing impact on the study of biological systems. 

Here, we will briefly discuss the essential features of the D-NEMD approach and how it can be used in a more general setting to study proteins. We also provide examples of different biomolecular systems and biological questions that can be addressed using this method. The examples, covering different proteins and a range of biological questions, demonstrate the versatility and general applicability of the D-NEMD approach and how it can provide a comprehensive and unbiased mapping of the structural responses and communication networks in proteins.

Short CV:

Sofia Oliveira is a computational biological chemist investigating protein structure, function and dynamics using computational approaches. Her research to date has been focused on understanding how dynamic and conformational changes in proteins modulate function. She received her degree in Chemical Engineering and her PhD in Biochemistry from the NOVA University Lisbon, Portugal. In 2017, she moved to the University of Bristol as a senior research associate working with Prof. Adrian Mulholland. In 2022, Oliveira was awarded a prestigious fellowship from the Biotechnology and Biological Sciences Research Council, and she is currently a Discovery Fellow at the University of Bristol. Oliveira is the author of more than 45 publications in peer-review journals and pre-prints (more details can be found at orcid: 0000-0001-8753-4950). Besides being a scientific researcher, Sofia is a mother of two and has a Portuguese water dog named Bartolomeu.