The Energy Landscape of Myoglobin:  An Optical Study

Leeson, Daan Thorn; Wiersma, Douwe A.; Fritsch, Klaus; Friedrich, J.

doi:10.1021/jp970908k

Cited by 93 publications

(37 citation statements)

References 29 publications

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“…Each statistical substate again contains more valleys. These lowertier substates, not shown, were also discovered experimentally (9). While these experimental data unambiguously demonstrate the inhomogeneity of proteins as described by the energy landscape, they provide only a crude insight into the full complexity.…”

Section: Conformation Space and Energy Landscapementioning

confidence: 53%

Protein dynamics and function: Insights from the energy landscape and solvent slaving

2007

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SummaryProtein motions are complex and a good way to describe them is in terms of a very high-dimensional conformation space. We give here a simple explanation of the conformation space and the energy landscape, the conformational motions and protein reactions, based on an analogy to a traffic problem. The analogy provides insight into the slaving of protein processes to bulk solvent fluctuations, in both the native and unfolded states.

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Section: Conformation Space and Energy Landscapementioning

confidence: 53%

Protein dynamics and function: Insights from the energy landscape and solvent slaving

2007

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“…A 0 dominates at low pH and is involved in NO enzymatics (27). (28). Above Ϸ170 K some very fast processes (k Ͼ 10 9 s Ϫ1 Ͼ Ͼ k diel ) are seen in inelastic neutron scattering and Möss-bauer experiments (19)(20)(21).…”

Section: The Energy Landscapementioning

confidence: 99%

Slaving: Solvent fluctuations dominate protein dynamics and functions

Fenimore

Frauenfelder

McMahon

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

640

558

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Protein motions are essential for function. Comparing protein processes with the dielectric fluctuations of the surrounding solvent shows that they fall into two classes: nonslaved and slaved. Nonslaved processes are independent of the solvent motions; their rates are determined by the protein conformation and vibrational dynamics. Slaved processes are tightly coupled to the solvent; their rates have approximately the same temperature dependence as the rate of the solvent fluctuations, but they are smaller. Because the temperature dependence is determined by the activation enthalpy, we propose that the solvent is responsible for the activation enthalpy, whereas the protein and the hydration shell control the activation entropy through the energy landscape. Bond formation is the prototype of nonslaved processes; opening and closing of channels are quintessential slaved motions. The prevalence of slaved motions highlights the importance of the environment in cells and membranes for the function of proteins.. . . everything that living things do can be understood in terms of the jigglings and wigglings of atoms.R. P. Feynman (1) P roteins perform most of the functions of living things, from metabolism to thinking. Textbooks usually show proteins naked, neglect fluctuations, and take little notice of the protein environment. Real proteins, however, are wiggling and jiggling, dressed by the hydration shell, and embedded in a cell or cell membrane. Feynman (1) stated the central problem succinctly, namely understanding protein functions in terms of the atomic motions. We are still very far from this goal, but progress is being made. Here we consider the effect of solvent fluctuations on protein processes. We will show that protein motions can be nonslaved or slaved. Nonslaved motions are independent of the solvent fluctuations. Slaved motions have rates that are proportional to the fluctuation rate of the solvent, but are smaller. We introduce a model, based on the energy landscape of the protein, that suggests how the protein controls its slaved dynamics. We use myoglobin (Mb) as a prototype, but the concepts apply also to many other proteins. The Dichotomy of MotionsThe main result of the present article emerges when the temperature dependences of protein processes are compared with the dielectric relaxation rate coefficient k diel (T) (2) of the solvent, essentially the average tumbling rate of the solvent water molecules. Fig. 1 shows k diel (T) (2) and the rate coefficients for various processes in Mb embedded in a 3:1 (vol͞vol) glycerol͞ water solvent (3-7). [We do not consider vibrations here, which can be described by normal modes (8).] We characterize the rate coefficients for selected processes by using the Inset in Fig. 1. The Inset shows a cross section through part of Mb with a heme group situated in the heme cavity and a major cavity called Xe-1 and labeled D. Small ligands such as carbon monoxide (CO) bind covalently at the heme iron. We denote the position of the CO by S if it is in the solvent, by A i...

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“…They are inhomogeneous, governed by an EL (4,20), and exhibit two types of fluctuations, ␣ and ␤, also called primary and secondary relaxation processes (21)(22)(23), with rate coefficients k ␣ (T) and k ␤ (T). Both also show relaxation phenomena at liquid helium temperatures (24). k ␣ (T) can be approximated by a Vogel-TammannFulcher relation,…”

Section: Protein Fluctuations and The Msdmentioning

confidence: 99%

“…The ␤-fluctuations, given by k ␤ (T) , are transitions between CS1␤. Below the CS1␤ are at least two more tiers (24,58). Presumably, the hierarchical arrangement of substates is responsible for control of functionally important protein motions (59).…”

Section: The Energy Landscapementioning

confidence: 99%

Bulk-solvent and hydration-shell fluctuations, similar to α- and β-fluctuations in glasses, control protein motions and functions

Fenimore

Frauenfelder²,

McMahon³

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

507

504

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The concept that proteins exist in numerous different conformations or conformational substates, described by an energy landscape, is now accepted, but the dynamics is incompletely explored. We have previously shown that large-scale protein motions, such as the exit of a ligand from the protein interior, follow the dielectric fluctuations in the bulk solvent. Here, we demonstrate, by using mean-square displacements (msd) from Mö ssbauer and neutron P roteins are the molecules that perform most biological functions, from storage of dioxygen (O 2 ) to enzyme catalysis. A central goal of protein science is to relate structure, dynamics, and function. Although investigations of protein structures and functions are well organized industries, protein dynamics is still in its infancy. Dynamics studies are best performed on proteins whose structures and functions are well known, e.g., myoglobin (Mb), the protein that gives muscles their red color. A hybrid picture of Mb is shown in Fig. 1. The lower part displays a piece of the protein backbone, namely, three ␣-helices. The upper part presents a space-filling view of the protein atoms. The active center, a heme group with a central iron atom, is red. Two cavities are also shown, Xe1 and the heme cavity. The protein is surrounded by the hydration shell, one to two layers of water, and is embedded in the bulk solvent. In Mb's role as an oxygenstorage protein, O 2 enters the protein, stays some time in Xe1, then binds at the heme iron (1). CO follows a similar path through the protein. The structure of Mb shows no permanent channel that leads from the outside to either Xe1 or the heme pocket or from Xe1 to the heme pocket. Thus, structural fluctuations are necessary for function (2).Fluctuations imply that Mb possesses numerous different conformations, called conformational substates (CS) (3). The different CS can be described by an energy landscape (EL) (4), the central concept in the folding (5), dynamics, and function of proteins. The EL is a construct in Ϸ3N dimensions, where N is the number of atoms forming the protein and the hydration shell. A substate is a point in this hyperspace, and structural fluctuations are represented by jumps between points. Initially, we assumed that protein conformations could be organized into a simple, rough EL (1). Experiments showed, however, that there are wells within wells within wells, and an organization of the EL with several tiers of decreasing free-energy barriers ensued (6). The top tier, denoted by CS0, contains a small number of CS with different structures that can have different functions: in A 0 Mb is involved in NO enzymatics; in A 1 it acts as an oxygen-storage system (7). Each of the CS0 substates can assume a very large number of CS1, called statistical substates. They perform the same function but with different rates. Here, we will show that the statistical substates comprise two tiers, CS1␣ and CS1␤. Fluctuations between CS1␣ substates are slaved to the solvent motions and involve sizeable structural changes (8). ...

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The Energy Landscape of Myoglobin: An Optical Study

Cited by 93 publications

References 29 publications

Protein dynamics and function: Insights from the energy landscape and solvent slaving

Protein dynamics and function: Insights from the energy landscape and solvent slaving

Slaving: Solvent fluctuations dominate protein dynamics and functions

Bulk-solvent and hydration-shell fluctuations, similar to α- and β-fluctuations in glasses, control protein motions and functions

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