Accurate Prediction of Protein NMR Spin Relaxation by Means of Polarizable Force Fields. Application to Strongly Anisotropic Rotational Diffusion

2020 ◽  
Vol 124 (25) ◽  
pp. 5103-5112 ◽  
Author(s):  
Moreno Marcellini ◽  
Minh-Ha Nguyen ◽  
Marie Martin ◽  
Maggy Hologne ◽  
Olivier Walker
Keyword(s):  
Spin Relaxation ◽  
Force Fields ◽  
Rotational Diffusion ◽  
Protein Nmr ◽  
Accurate Prediction ◽  
Polarizable Force Fields ◽  
Nmr Spin Relaxation ◽  
Anisotropic Rotational Diffusion

scholarly journals Effects of Hydrogen Bonding on the Rotational Dynamics of Water-Like Molecules in Liquids: Insights from Molecular Dynamics Simulations

2020 ◽  
Vol 73 (8) ◽  
pp. 734
Author(s):  
W. A. Monika Madhavi ◽  
Samantha Weerasinghe ◽  
Konstantin I. Momot
Keyword(s):  
Molecular Dynamics ◽  
Hydrogen Bonding ◽  
Hydrogen Sulfide ◽  
Spin Relaxation ◽  
Rotational Diffusion ◽  
Molecular Geometry ◽  
Md Simulations ◽  
Water Molecules ◽  
Molecular Reorientation ◽  
Nmr Spin Relaxation

Rotational motion of molecules plays an important role in determining NMR spin relaxation properties of liquids. The textbook theory of NMR spin relaxation predominantly uses the assumption that the reorientational dynamics of molecules is described by a continuous time rotational diffusion random walk with a single rotational diffusion coefficient. Previously we and others have shown that reorientation of water molecules on the timescales of picoseconds is not consistent with the Debye rotational-diffusion model. In particular, multiple timescales of molecular reorientation were observed in liquid water. This was attributed to the hydrogen bonding network in water and the consequent presence of collective rearrangements of the molecular network. In order to better understand the origins of the complex reorientational behaviour of water molecules, we carried out molecular dynamics (MD) simulations of a liquid that has a similar molecular geometry to water but does not form hydrogen bonds: hydrogen sulfide. These simulations were carried out at T=208K and p=1 atm (~5K below the boiling point). Ensemble-averaged Legendre polynomial functions of hydrogen sulfide exhibited a Gaussian decay on the sub-picosecond timescale but, unlike water, did not exhibit oscillatory behaviour. We attribute these differences to hydrogen sulfide’s absence of hydrogen bonding.

Molecular Dynamics Using Non-Variational Polarizable Force Fields: Theory, Periodic Boundary Conditions Implementation and Application to the Bond Capacity Model

2019 ◽  
Author(s):  
Pier Paolo Poier ◽  
Louis Lagardere ◽  
Jean-Philip Piquemal ◽  
Frank Jensen
Keyword(s):  
Boundary Conditions ◽  
Periodic Boundary ◽  
Force Fields ◽  
Periodic Boundary Conditions ◽  
Computational Effort ◽  
Polarizable Force Fields ◽  
Energy Models ◽  
Capacity Model ◽  
Energy Gradient ◽  
Polarization Models

<div> <div> <div> <p>We extend the framework for polarizable force fields to include the case where the electrostatic multipoles are not determined by a variational minimization of the electrostatic energy. Such models formally require that the polarization response is calculated for all possible geometrical perturbations in order to obtain the energy gradient required for performing molecular dynamics simulations. </p><div> <div> <div> <p>By making use of a Lagrange formalism, however, this computational demanding task can be re- placed by solving a single equation similar to that for determining the electrostatic variables themselves. Using the recently proposed bond capacity model that describes molecular polarization at the charge-only level, we show that the energy gradient for non-variational energy models with periodic boundary conditions can be calculated with a computational effort similar to that for variational polarization models. The possibility of separating the equation for calculating the electrostatic variables from the energy expression depending on these variables without a large computational penalty provides flexibility in the design of new force fields. </p><div><div><div> </div> </div> </div> <p> </p><div> <div> <div> <p>variables themselves. Using the recently proposed bond capacity model that describes molecular polarization at the charge-only level, we show that the energy gradient for non-variational energy models with periodic boundary conditions can be calculated with a computational effort similar to that for variational polarization models. The possibility of separating the equation for calculating the electrostatic variables from the energy expression depending on these variables without a large computational penalty provides flexibility in the design of new force fields. </p> </div> </div> </div> </div> </div> </div> </div> </div> </div>

scholarly journals High-resolution mining of the SARS-CoV-2 main protease conformational space: supercomputer-driven unsupervised adaptive sampling

2021 ◽  
Author(s):  
Théo Jaffrelot Inizan ◽  
Frédéric Célerse ◽  
Olivier Adjoua ◽  
Dina El Ahdab ◽  
Luc-Henri Jolly ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
High Resolution ◽  
Adaptive Sampling ◽  
Force Fields ◽  
Sampling Strategy ◽  
Md Simulations ◽  
Conformational Space ◽  
Many Body ◽  
Polarizable Force Fields ◽  
Main Protease

We provide an unsupervised adaptive sampling strategy capable of producing μs-timescale molecular dynamics (MD) simulations of large biosystems using many-body polarizable force fields (PFFs).

scholarly journals The Role of Electrostatics in Enzymes: Do Biomolecular Force Fields Reflect Protein Electric Fields?

2020 ◽  
Author(s):  
Richard T Bradshaw ◽  
Jacek Dziedzic ◽  
Chris-Kriton Skylaris ◽  
Jonathan W. Essex
Keyword(s):  
Electric Fields ◽  
Active Sites ◽  
Catalytic Mechanism ◽  
Force Fields ◽  
Prolyl Isomerase ◽  
Peptidyl Prolyl Isomerase ◽  
Polarizable Force Field ◽  
Polarizable Force Fields ◽  
Protein Active Sites ◽  
Dynamics Simulations

<div><div><div><p>Preorganization of large, directionally oriented, electric fields inside protein active sites has been proposed as a crucial contributor to catalytic mechanism in many enzymes, and may be efficiently investigated at the atomistic level with molecular dynamics simulations. Here we evaluate the ability of the AMOEBA polarizable force field, as well as the additive Amber ff14SB and Charmm C36m models, to describe the electric fields present inside the active site of the peptidyl-prolyl isomerase cyclophilin A. We compare the molecular mechanical electric fields to those calculated with a fully first principles quantum mechanical (QM) representation of the protein, solvent, and ions, and find that AMOEBA consistently shows far greater correlation with the QM electric fields than either of the additive force fields tested. Catalytically-relevant fields calculated with AMOEBA were typically smaller than those observed with additive potentials, but were generally consistent with an electrostatically-driven mechanism for catalysis. Our results highlight the accuracy and the potential advantages of using polarizable force fields in systems where accurate electrostatics may be crucial for providing mechanistic insights.</p></div></div></div>

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