Dispersion Forces and the Molecular Origin of Internal Friction in Protein

Abstract

Internal friction in macromolecules is one of the curious phenomena that control conformational changes and reaction rates. It is held here that dispersion interactions and London-van der Waals forces between nonbonded atoms are major contributors to internal friction. To demonstrate this, the flipping motion of aromatic rings of F10 and Y97 amino acid residues of cytochrome c has been studied in glycerol/water mixtures by cross relaxation-suppressed exchange nuclear magnetic resonance spectroscopy. The ring-flip rate is highly overdamped by glycerol, but this is not due to the effect of protein-solvent interactions on the Brownian dynamics of the protein, because glycerol cannot penetrate into the protein to slow the internal collective motions. Sound velocity in the protein under matching solvent conditions shows that glycerol exerts its effect by rather smothering the protein interior to produce reduced molecular compressibility and root-mean-square volume fluctuation (δVRMS), implying an increased number of dispersion interactions of nonbonded atoms. Hence, δVRMS can be used as a proxy for internal friction. By using the ansatz that internal friction is related to nonbonded interactions by the equation f(n) = f0 + f1n + f2n(2) + ..., where the variable n is the extent of nonbonded interactions with fi coefficients, the barrier to aromatic ring rotation is found to be flat. Also interesting is the appearance of a turnover region in the δVRMS dependence of the ring-flip rate, suggesting anomalous internal diffusion. We conclude that cohesive forces among nonbonded atoms are major contributors to the molecular origin of internal friction.

V67L Mutation Fills an Internal Cavity To Stabilize RecA Mtu Intein

“…21,22 In addition, filling the cavity and increasing the density of the protein interior can increase the number of dispersion interactions among nonbonded atoms to increase stability. 23 Although cavity shapes are visibly different in ΔΔIhh-L67 and ΔΔIhh-V67 (Figure 1) crystal structures, the cavity sizes in solution cannot be accurately assessed from crystal structures alone, because of the dynamics and ensemble behavior of protein cavities in solution. These considerations motivated us to perform solution NMR studies of ΔΔIhh-V67 and ΔΔIhh-L67 at high pressures to quantify the change in the volume of folding.…”

“…Imperfect packing in folded proteins creates internal cavities, primarily surrounded by hydrophobic side chains. It has been shown through crystallography, ultraviolet (UV) absorbance, fluorescence, and NMR that mutations that increase cavity size can decrease the stability of the protein fold − while smaller cavities can lead to higher stability. , In addition, filling the cavity and increasing the density of the protein interior can increase the number of dispersion interactions among nonbonded atoms to increase stability . Although cavity shapes are visibly different in ΔΔIhh-L67 and ΔΔIhh-V67 (Figure ) crystal structures, the cavity sizes in solution cannot be accurately assessed from crystal structures alone, because of the dynamics and ensemble behavior of protein cavities in solution.…”

Temperature Dependence of Internal Friction of Peptides

“…Internal friction is a widely used concept to characterize the dissipations of various systems in solids, liquids, polymers, and even a single molecule. − During recent decades, internal friction in protein systems has attracted long-lasting interest. The characteristics of internal friction in protein systems become an appealing topic in the studies on the connections between the interactions and dynamics of proteins.…”

Rouse model with fluctuating internal friction

“…The presence of an additional mode of dissipation in polymer molecules arising from intramolecular interactions, denoted as internal friction or internal viscosity [1][2][3][4][5][6][7] , has been invoked to reconcile the high values of dissipated work observed in force spectroscopic measurements on single molecules [8][9][10][11] , the steepness of the probability distribution of polymer extensions in coil-stretch transitions observed in turbulent flow 12 , and the dampened reconfiguration kinetics of biopolymers [13][14][15][16][17][18][19][20][21][22][23][24][25] . The discontinuous jump in the stress in polymer solutions upon the inception or cessation of flow 26,27 has also been attributed to internal friction.…”