Variation of Energy Transfer Rates across Protein–Water Contacts with Equilibrium Structural Fluctuations of a Homodimeric Hemoglobin

Abstract

Molecular dynamics simulations of the homodimeric hemoglobin from Scapharca inaequivalvis (HbI) have been carried out to examine relations between rates of vibrational energy transfer across nonbonded contacts and equilibrium structural fluctuations, with emphasis on protein−water contacts. The scaling of rates of energy transfer with equilibrium fluctuations of the contact length is found to hold up well for contacts between residues and hemes at the interface and the cluster of 17 interface water molecules in the unliganded state of HbI, as well as for the liganded state, for which the cluster contains on average 11 water molecules. In both states, the rate of energy transfer is also found to satisfy a diffusion relation. Within each globule, the scaling for polar contacts is similar to that found in an earlier analysis of myoglobin. Entropy associated with dynamics of polar contacts within each globule and with contacts between the hemes and water cluster is found to increase upon ligation. Energy exchange networks (EENs) for liganded and unliganded states obtained from the simulations are also presented and discussed. Energy transport networks through which nonbonded contacts transport energy in HbI, referred to as nonbonded networks (NBNs), are determined from the EENs and compared for the two states.

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

“…We again found that, for non-bonded contacts interacting by short-range potentials, the energy transfer rate across the contact varies inversely with the variance in the contact length. A similar relation was found for the hydrogen-bonded contacts of the dimeric hemoglobin from Scapharca Inaequivalvis, HbI, in the unliganded state, including contacts with water molecules at the interface of the two globules (Leitner et al 2019;Reid et al 2020).…”

“…The data appear to fall on two lines for different sets of polar contacts. The contacts represented by the orange data points and the contacts represented by the blue data points are detailed in (Reid et al 2020); (b) Energy conductivity, G, between the cluster of water molecules at the interface of deoxy-HbI and either the heme or residues at the interface as a function of the inverse of the variance, 〈δr 2 〉 −1 , in the length of that contact. The data plotted in purple, which fall near the line with greater slope, correspond to hydrogen bonding between the heme and water molecules at the interface.…”

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

“…Networks of residues that transport energy have been obtained via computation of local energy diffusion coefficients, − estimated from the results of normal-mode analysis and related to thermal transport coefficients, − as well as computation of local energy currents obtained from time-correlation functions of the energy flux between residues. ,, We carry out the latter approach, developed by Yamato and co-workers, in this study. Energy exchange networks (EENs) , are obtained as the intersection of relatively large rates of energy transfer between residues. , The rates of energy transfer are related to the equilibrium dynamics of the contacts ,,− and can be measured by a number of time-resolved spectroscopic techniques. − We note that at such a coarse-grained level master equation simulations have modeled well the transport of energy when compared with the results of all-atom nonequilibrium MD simulations. , …”

Energy flow and intersubunit signalling in GSAM: A non-equilibrium molecular dynamics study

“…In the current study, one water molecule in the cluster was found to have a persistent hydrogen-bond with KE4, allowing it to receive and transmit energy across the cluster and beyond. Previous studies of vibrational energy transport rates on homodimeric hemoglobin (HbI) [75] , [76] have shown that small water clusters between the dimer interfaces enhance energy transport, as they receive energy at a higher rate from locally hot regions due to the higher thermal conductivity of water relative to amino acids, thus playing an essential role as an energy conduit in the biomolecule.…”