Understanding the Structure and Dynamics of Peptides and Proteins Through the Lens of Network Science
Mathieu Fossepré, Laurence Leherte, Aatto Laaksonen, Daniel P. Vercauteren · Methods and principles in medicinal chemistry · 2018
Over the past decades, network science has been applied to the study of various complex systems in numerous domains, such as sociology and telecommunication, and also biology and chemistry. Particularly, network science opened the way to a new understanding of the structural and dynamics properties of biological systems at different spatial and temporal scales. The aim of the review is to report typical examples of network science applications in the field of small peptides and protein structure, dynamics, and function. After an introduction on the importance of networks to today's science, the review focuses on network analyses of static protein structures as topological features of protein structure networks are related to their relevant functional aspects. Then, the review describes how dynamical properties of proteins, such as complex conformational changes, can be tracked by networking molecular simulations data or using dynamical networks. In this context, we discuss strong relationships between network science and coarse-grained modeling. Next, we describe how network modularization techniques could pave the way for innovative multiscale and modular models of proteins. Regarding our contributions to the field of network science, we (i) very briefly resume several applications using graphs to consider inorganic three-dimensional networks and small organic molecules, (ii) show that graph reductions of three-dimensional molecular fields are helpful for alignments of ligands and their subsequent molecular similarity evaluation in general, and (iii) summarize our studies on the intrinsic flexibility properties of a protein through the design of original multiscale coarse-grained elastic network models. The µ-opioid receptor, a G protein–coupled receptor (GPCR), the target for most anesthesia drugs, is taken into account as an example structure for most concepts and ideas reviewed all along in the manuscript.