The coupling of thermodynamics with the organizational water-protein intra-dynamics driven by the H-bonds dissipative potential of cluster water

TL;DR

This paper explores how water-protein intra-dynamics driven by hydrogen bonds influence thermodynamic processes in hemoglobin, affecting oxygen and ion binding, with implications for understanding cellular sensing and hydration mechanisms.

Contribution

It introduces a novel model linking water cluster dissipation potential to hemoglobin conformational changes and thermodynamics, integrating hydration dynamics with protein function.

Findings

Water cluster dissipation influences hemoglobin conformational states.

Hydration shells modulate activation energy peaks and transition states.

Water dynamics affect oxygen and ion binding in blood proteins.

Abstract

The Red cell-Hb-CSF functions as a sensor adapting response to Hb heterotropic equilibriums. At the lungs O2 and Mg2+, each one increasing affinity for the other stabilize the relax (R) form [(O2)4Hb(Mg)2].(H2O)R. At tissue level, the inclusion of H+ and 2,3-DPG excludes O2 and Mg2+ to stabilize the tense (T) form 2,3-DPG-deoxyHb-(H2O)T. Both senses are integrated into a cycle T into R and R into T, without involving a direct reversal. The dissipative potential of water cluster (H2O)n interacts with the hydrophilic asymmetries of Hb, to restrict randomness of the kinetic sense implicated in a single peak for activation energy (Ea). The hydration shells could sequence an enhanced Ea into several peaks, to sequentially activate transitions states. Hence, changes in dipole state, sliding, pKa, n-H-bonds, etc., could became concatenated for vectoriality. (H2O)n by the loss of H-bonds couple with to the hydration turnover of proteins and ions to result in incomplete water cluster (H2O)n*, with a lower-n. (H2O)n* became a carrier of heat/entropy into the cerebrospinal fluid (CSF) which has to be replaced 3.7 times per day. OxyHb formation involves sliding-down of alpha vs beta chains, to shift alpha1 and alpha2 Pro 44 into allowing the entrance of a fully hydrated [Mg.(H2O)6](H2O)12-14(2+) (or Zn2+) into the hydrophilic beta2-alpha1 and beta1-alpha2 interfaces. OxyHb pKa of 6.4 leads to H+-dissociation increasing negative charge of R-groups. This at beta2-alpha1 sequence two tetradentate chelates, first an Mg2+, bonding with beta2 His 92 and a second Mg2+ with alpha1 His 87, to cooperatively release hindrance. The interconversion of oxy-to-deoxyHb, pKa=8, leads to the amphoteric imidazole to became positively charged and proximal histidines return into hindrance position, releasing the incomplete hydrated Mg.(H2O)inc(2+) and O2 into CSF.