Dynamics of Methionine Ligand Rebinding in Cytochrome c

Abstract

Geminate recombination of the methionine ligand to the heme iron in ferrous cytochrome c protein following photodissociation displays rich kinetics. It is of particular interest to develop an understanding of fast and slow rebinding time scales, observed in experimental studies, in terms of features of the underlying complex energy landscape. The classical empirical force field in the heme pocket has been extended by incorporating ab initio potential energy surface calculations representing the ground singlet state and quintet state associated with methionine bond breaking and rebinding. An algorithm based on the Landau−Zener nonadiabatic transition theory has been employed to model the electronic surface hopping between two spin states during the process of ligand dissociation and recombination. Multiple conformational substates of the dissociated methionine ligand are found to participate in the reaction dynamics. Varying time scales for interconversion between substates lead to a mechanism elucidating the fast and slow rebinding time scales. The reaction system may be understood in terms of a two-dimensional reaction coordinate distinctly separated from the coupled bath of surrounding protein and solvent degrees of freedom. Insights into the reaction dynamics provided by this study lead to suggestions for future experiments to further probe the role of dynamic heterogeneity in the kinetics of ligand−protein binding. ■ INTRODUCTIONGeminate recombination of axial ligands to the iron atom in heme proteins, as one of the key steps of protein global structural dynamics and allostery, has been of great interest and widely studied both experimentally and theoretically in the past decades. Many of those studies have been dedicated to diatomic axial ligands, such as CO, NO, and O 2 in globins.1−27 From those studies, a deep and general understanding of protein dynamics, in terms of transitions between conformational substates, has developed and formed the foundation for modern "energy landscape" theories of protein dynamics and thermodynamics. In spite of this success, a rigorous understanding of molecular reaction dynamics for ligand rebinding in myoglobin has proven elusive. The Agmon−Hopfield 8 and Champion-Srajer 28,29 models of ligand rebinding define specific reaction coordinates for the rebinding process but also include an undefined protein coordinate as an essential component of the multidimensional reaction coordinate in addition to the surrounding bath. Although heme−ligand dissociation in heme proteins usually does not occur under normal conditions, heme−ligand bond breaking and rebinding take place during the process of internal and external ligand switching or competition in neuroglobin 30,31 as well as in a specific group of heme-based sensor proteins such as Ec DOS, DOSH, and CooA. 7,32,33 Understanding the kinetics and thermodynamics of internal ligand binding is essential to our knowledge of the composition and function of these heme proteins.Cytochrome c (cyt c) (Figure 1) is an essential ...

Formation of Oil/Water Interface by Mixed Surface Active Ionic Liquid-Ethoxylated Alkyl Ether: Energetics, Microstructures, Solvation Dynamics, and Antimicrobial Activity

“…Electrical conductance is sensitive to local dropletdroplet interactions and structural changes of surfactant aggregates. [43][44][45] In continuation of comparative studies on the structure of mixed SAIL/Brij-58 microemulsions, in the present report, we further delineated the influence of water content and the chemical architecture of cosurfactant molecules on the transport properties of mixed microemulsions. Among the physicochemical properties of w/o microemulsions, the percolation of conductance is noteworthy where a several fold increase in conductance takes place after threshold water content at constant temperature or after a threshold temperature at constant composition.…”

“…Consequently, the packing ratio of the surfactant molecules increases, and thereby the radius of the droplets decreases. [45] 4 ] has already been confirmed by DLS measurement. In order to obtain more insights into the microstructure of the mixed microemulsions, we choose to monitor the microenvironment or water dynamics inside nanowater pool by FT-IR technique, which has been discussed subsequently.…”

“…Therefore, the highest rigidity of the interfacial film and the very weak interdroplet attractive interactions make the droplets' collision and fusion difficult, and thus delayed percolation is noticed in the C 16 mimCl/Brij-58/1-Pn/water systems. [45] The results of the effect of short chain RTIL ([bmim][BF 4 ]) on the percolation of conductance in mixed C 16 mimCl/Brij-58 systems in Hp as a function of water content (w) have also been presented in Figure 4B. It has been observed that the addition of ILs significantly increases w p , i. e., retards percolation.…”

“…The interfacial layers are made up of cosurfactant and surfactant, having their polar head groups in contact with the water and their alkyl chains pointed toward the oil. [45] The penetration ability is related to the alkyl chain configuration of cosurfactant molecules. The cosurfactant with branched chain has lower penetration ability to the oil/water interface compared to their unbranched analogues.…”

Experimental and Theoretical Efforts to Identify the Microstructural Transition of Water to Acetonitrile‐Based Reverse Micelle through Binary Compositions of Polar Solvents

“…Moreover, the interdroplet attractive interactions become stronger with increasing concentration of ACN, and the droplets become more interconnected and easily form the transient channel for ions transfer with increasing polar solvent content, and thus the conductivity is increased sharply. [29] Thus, it can be summarized from the following results that conductance behaviour in DDAB RMs containing 100% to 60% water (w 0 = 3.70-2.22) as polar phase governed by the counter-balancing effects of two mechanisms (i.e., "hopping" and "fusion-fission"); whereas charge migration mechanism through interconnected droplets played important role for 50% to water to 100% ACNbased (w 0 = 1.85-0) DDAB RMs. These results pointed out that a structural transition in DDAB RMs occurred at a particular composition of polar solvent, i.e., 50% of water (v/v) or w 0 of 1.85.…”