scholarly journals Role of Electrostatic Interactions in the Isoform-Specific Rate of ADP Release from Human Cardiac Myosin

2018 ◽  
Vol 114 (3) ◽  
pp. 140a-141a
Author(s):  
Akhil Gargey ◽  
Jinghua Ge ◽  
Yaroslav Tkachev ◽  
Yuri Nesmelov
Keyword(s):  
Electrostatic Interactions ◽  
Specific Rate ◽  
Cardiac Myosin ◽  
Adp Release

scholarly journals The time of strong actomyosin binding depends on electrostatic interactions within the force generating region in human cardiac myosin

2020 ◽  
Author(s):  
Akhil Gargey ◽  
Shiril Bhardwaj Iragavarapu ◽  
Alexander V. Grdzelishvili ◽  
Yuri E. Nesmelov
Keyword(s):  
Electrostatic Interactions ◽  
Myosin Head ◽  
Bound State ◽  
Myosin Isoforms ◽  
Salt Bridges ◽  
Cardiac Myosin ◽  
Wild Type ◽  
Transient Kinetics ◽  
Adp Release ◽  
Dynamics Simulations

AbstractTwo single mutations, R694N and E45Q, were introduced in the beta isoform of human cardiac myosin to remove permanent salt bridges E45:R694 and E98:R694 in the force-generating region of myosin head. Beta isoform-specific bridges E45:R694 and E98:R694 were discovered in the molecular dynamics simulations of the alpha and beta myosin isoforms. Alpha and beta isoforms exhibit different kinetics, ADP dissociates slower from actomyosin containing beta myosin isoform, therefore, beta myosin stays strongly bound to actin longer. We hypothesize that the electrostatic interactions in the force-generating region modulate affinity of ADP to actomyosin, and therefore, the time of the strong actomyosin binding. Wild type and the mutants of the myosin head construct (1-843 amino acid residues) were expressed in differentiated C2C12 cells, and duration of the strongly bound state of actomyosin was characterized using transient kinetics spectrophotometry. All myosin constructs exhibited a fast rate of ATP binding to actomyosin and a slow rate of ADP dissociation, showing that ADP release limits the time of the strongly bound state of actomyosin. Mutant R694N showed faster rate of ADP release from actomyosin, compared to the wild type and the E45Q mutant, thus confirming that electrostatic interactions within the force-generating region of human cardiac myosin regulate ADP release and the duration of the strongly bound state of actomyosin.

scholarly journals Electrostatic Interactions Within Loop 1 and the Force Generation Region of Human Cardiac Myosin Affect the Rate of Actomyosin Dissociation and ADP Release

2019 ◽  
Vol 116 (3) ◽  
pp. 259a-260a
Author(s):  
Akhil Gargey ◽  
Jinghua Ge ◽  
Alex Grdzelishvili ◽  
Yaroslav Tkachev ◽  
Yuri E. Nesmelov
Keyword(s):  
Electrostatic Interactions ◽  
Force Generation ◽  
Cardiac Myosin ◽  
Adp Release ◽  
Generation Region

scholarly journals Electrostatic interaction of loop 1 and backbone of human cardiac myosin regulates the rate of ATP induced actomyosin dissociation

2021 ◽  
Author(s):  
Akhil Gargey Iragavarapu ◽  
Yuri Nesmelov
Keyword(s):  
Electrostatic Interactions ◽  
Myosin Head ◽  
Salt Bridge ◽  
C2c12 Cells ◽  
Atp Binding ◽  
Cardiac Myosin ◽  
Wild Type ◽  
Transient Kinetics ◽  
Double Mutation ◽  
Adp Release

Double mutation D208Q:K450L was introduced in the beta isoform of human cardiac myosin to remove the salt bridge D208:K450 connecting loop 1 and the seven stranded beta sheet within the myosin head. Beta isoform specific salt bridge D208:K450 was previously discovered in the molecular dynamics simulations. It was proposed that loop 1 modulates nucleotide affinity to actomyosin and we hypothesized that the electrostatic interactions between loop 1 and myosin head backbone regulates ATP binding to and ADP dissociation from actomyosin, and therefore, the time of the strong actomyosin binding. Wild type and the mutant of the myosin head construct (843 amino acid residues) were expressed in differentiated C2C12 cells, and the kinetics of ATP induced actomyosin dissociation and ADP release were characterized using transient kinetics spectrophotometry. Both constructs exhibit a fast rate of ATP binding to actomyosin and a slow rate of ADP dissociation, showing that ADP release limits the time of the strongly bound state of actomyosin. We observed a faster rate of ATP induced actomyosin dissociation with the mutant, compared to the wild type actomyosin. The rate of ADP release from actomyosin remains the same for the mutant and the wild type actomyosin. We conclude that the flexibility of loop 1 is a factor affecting the rate of ATP binding to actomyosin and actomyosin dissociation. We observed no effect of loop 1 flexibility on the rate of ADP release from actomyosin.

The Role of Electrostatic Interactions in Protease Surface Diffusion and the Consequence for Interfacial Biocatalysis

Langmuir ◽  
2010 ◽  
Vol 26 (24) ◽  
pp. 18916-18925 ◽  
Author(s):  
Bob E. Feller ◽  
James T. Kellis ◽  
Luis G. Cascão-Pereira ◽  
Channing R. Robertson ◽  
Curtis W. Frank
Keyword(s):  
Surface Diffusion ◽  
Electrostatic Interactions

scholarly journals Role of Dispersion Attraction in Differential Geometry Based Nonpolar Solvation Models

2015 ◽  
Vol 3 (1) ◽  
Author(s):  
Zhan Chen
Keyword(s):  
Differential Geometry ◽  
Electrostatic Interactions ◽  
Polar Component ◽  
Great Success ◽  
Free Energies ◽  
Dispersion Interactions ◽  
Solvation Models ◽  
Nonpolar Solvation ◽  
Solvation Analysis

AbstractDifferential geometry (DG) based solvation models have shown their great success in solvation analysis by avoiding the use of ad hoc surface definitions, coupling the polar and nonpolar free energies, and generating solvent-solute boundary in a physically self-consistent fashion. Parameter optimization is a key factor for their accuracy, predictive ability of solvation free energies, and other applications. Recently, a series of efforts have been made to improve the parameterization of these new implicit solvent models. In thiswork, we aim at studying the role of dispersion attraction in the parameterization of our DG based solvation models. To this end, we first investigate the necessity of van derWaals (vdW) dispersion interactions in the model and then carry out systematic parameterization for the model in the absence of electrostatic interactions. In particular, we explore how the changes in Lennard-Jones (L-J) potential expression, its decomposition scheme, and choices of some fixed parameter values affect the optimal values of other parameters as well as the overall modeling error. Our study on nonpolar solvation analysis offers insights into the parameterization of nonpolar components for the full DG based models by eliminating uncertainties from the electrostatic polar component. Therefore, it can be regarded as a step towards better parameterization for the full DG based model.

Solvent effect on the conformational behavior of substituted spiro[4.5]decanes and spiro[5.5]undecanes

1995 ◽  
Vol 73 (5) ◽  
pp. 703-709 ◽  
Author(s):  
S. Sağ Erdem ◽  
T. Varnali ◽  
V. Aviyente ◽  
M.F. Ruiz-Lopez
Keyword(s):  
Solvent Effect ◽  
Electrostatic Interactions ◽  
Multipole Moment ◽  
Semiempirical Methods ◽  
Main Role ◽  
Solvent Interactions ◽  
Reaction Field ◽  
Solvent Models ◽  
Conformational Equilibria

We studied the relatively complex polar systems 6-substituted-1,4-dioxospiro[4.5]decanes and 7-substituted-1,5-dioxospiro[5.5]undecanes with substituents X = CH3, F, Cl, CN, OH, OCH3, and NO2. Solvent effects on the equilibrium have been analysed by means of a Self-Consistent-Reaction-Field model and the PM3 method. Complete geometry optimizations have been carried out for all the structures in the gas phase and in solution. For some substituents, a set of rotamers have been separately optimized. The discussion of the results is focussed on the effects arising from structural aspects and from steric and electrostatic interactions on the axial/equatorial relative stability. The role played by multipole moment is considered. In general, good agreement with available experimental data and with previous theoretical studies has been obtained. Though the use of semiempirical methods and simple solvent models prevents us from reaching definitive conclusions, this approach seems to be very useful in predicting the main role of solute–solvent interactions in conformational equilibria of complex systems for which ab initio calculations cannot be performed. Keywords: conformational equilibria, spiro decanes and undecanes, cavity model, SCRF, solvent effect, PM3 calculations.

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