Recent developments in the computational study of protein structural and vibrational energy dynamics

Abstract

Recent developments in the computational study of energy transport in proteins are reviewed, including advances in both methodology and applications. The concept of energy exchange network (EEN) is discussed, and a recent calculation of EENs for the allosteric protein FixL is reviewed, which illustrates how residues and protein regions involved in the allosteric transition can be identified. Recent work has examined relations between EENs and protein dynamics as well as structure. We review some of the computational studies carried out on several proteins that explore connections between energy conductivity across polar contacts in proteins and between proteins and water and equilibrium dynamics of the contacts, and we discuss some of the recent experimental work that addresses this topic.

Energy Bilocalization Effect and the Emergence of Molecular Functions in Proteins

“…We quote here in a non-exhaustive way some works that resonate perfectly with our description. First of all, we fully agree that in these systems, the diffusion of energy does not take place homogeneously, but rather along distinct paths connecting sub-regions of the protein (what we call here the valleys of confinement potential) giving rise to a transport by percolation ( Leitner and Yamato, 2020 ; Leitner, 2008 ). That is, energy can propagate from residue A to residue B if and only if these residues are part of a connex network defined by their mechanical coupling (cohesive energy).…”

“…This particular description of the energetic properties exposed here must be further discussed and confronted with previous studies. It is therefore appropriate to present in particular the work of Leitner et al (2015) with whom we share this idea that the origin of the functional properties of proteins and enzymes is intrinsically associated with the way in which a given structure is able to diffuse heat in the molecular scaffold ( Leitner and Yamato, 2020 ). His approach consists in calculating the local (i.e., residue scale) diffusion on the basis of atomistic simulations such as molecular dynamics.…”

“…Furthermore, Leitner’s works also showed that energy percolation between a catalytic residue and other distant residues allows the modulation of chemical bonds through thermal fluctuations (which results in the fluctuations in the length of hydrogen bonds) and that the corresponding network of connected residues correlate well with the mapping of energy flow ( Leitner and Yamato, 2020 ).…”

Activation-Induced Reorganization of Energy Transport Networks in the β2 Adrenergic Receptor

“…A variety of networks, including structure-based contact networks, ,− dynamic perturbation networks, and energy transport networks ,,, have been defined and studied to identify regions of a protein, including water, ,,− that play key roles in signaling and allosteric regulation. We focus on energy transport and contact networks in this study.…”

pyProGA—A PyMOL plugin for protein residue network analysis

“…PRNs were used for identification of efficient communication pathways and used to explain allostery effects in proteins and protein clusters [13][14][15] and were shown to be related to some physical phenomena [16,17]. An interesting topic is the study of Energy Exchange Networks for proteins as done by Leitner [18] Yamato and others [19][20][21]. Such and similar models evaluate heat/energy transfer, typically quantities used in continuum theories, over a discretized irregular mesh represented by the network.…”