scholarly journals Exploiting a Mechanical Perturbation of Titin Domain to Identify How Force Field Parameterization Affects Protein Refolding Pathways

2019 ◽  
Author(s):  
David Wang ◽  
Piotr E. Marszalek
Keyword(s):  
Force Field ◽  
Force Fields ◽  
Direct Transition ◽  
Mechanical Perturbation ◽  
Atomic Force ◽  
Force Field Parameterization ◽  
Helical Peptide ◽  
Perturbed Model ◽  
Simulation Time ◽  
Insight Into

AbstractMolecular mechanics force fields have been shown to differ in their predictions of processes such as protein folding. To test how force field differences affect predicted protein behavior, we created a mechanically perturbed model of the beta-stranded I91 titin domain based on atomic force spectroscopy data and examined its refolding behavior using six different force fields. To examine the transferability of the force field discrepancies identified by this model, we compared the results to equilibrium simulations of the weakly helical peptide Ac-(AAQAA)3-NH2. The total simulation time was 80 µs. From these simulations we found significant differences in I91 perturbation refolding ability between force fields. Concurrently, Ac-(AAQAA)3-NH2 equilibration experiments indicated that although force fields have similar overall helical frequencies, they can differ in helical lifetimes. The combination of these results suggests that differences in force field parameterization may allow a more direct transition between the beta and alpha regions of the Ramachandran plot thereby affecting both beta-strand refolding ability and helical lifetimes. Furthermore, the combination of results suggests that using mechanically perturbed models can provide a controlled method to gain more insight into how force fields affect protein behavior.

Molecular simulation of osmometry in aqueous solutions of the BMIMCl ionic liquid: a potential route to force field parameterization of liquid mixtures

2020 ◽  
Vol 22 (48) ◽  
pp. 28325-28338
Author(s):  
Debdas Dhabal ◽  
Tanmoy Patra
Keyword(s):  
Experimental Data ◽  
Aqueous Solution ◽  
Ionic Liquid ◽  
Aqueous Solutions ◽  
Force Field ◽  
Molecular Simulation ◽  
Osmotic Coefficient ◽  
Force Fields ◽  
Liquid Mixtures ◽  
Force Field Parameterization

By means of molecular simulation, the osmotic coefficient of aqueous solution of BMIMCl ionic liquid is calculated to compare with the experimental data and use that to optimize two popular force fields available in the literature for bulk ILs.

Development of accurate coarse-grained force fields for weakly polar groups by an indirect parameterization strategy

2021 ◽  
Vol 23 (11) ◽  
pp. 6763-6774
Author(s):  
Junjie Song ◽  
Mingwei Wan ◽  
Ying Yang ◽  
Lianghui Gao ◽  
Weihai Fang
Keyword(s):  
Force Field ◽  
Force Fields ◽  
Coarse Grained ◽  
Polar Groups ◽  
Force Field Parameterization

An indirect coarse-grained force field parameterization strategy for weakly polar groups.

Hydration Free Energies of Organic Molecules in the FreeSolv Database Calculated with Polarized Atom In Molecules Atomic Charges and the GAFF Force Field.

2018 ◽  
Author(s):  
Maximiliano Riquelme ◽  
Alejandro Lara ◽  
David L. Mobley ◽  
Toon Vestraelen ◽  
Adelio R Matamala ◽  
...  
Keyword(s):  
Force Field ◽  
Functional Groups ◽  
Electrostatic Interactions ◽  
Organic Molecules ◽  
Force Fields ◽  
Chemical Elements ◽  
Atomic Charges ◽  
Free Energies ◽  
Molecular Systems ◽  
Solvent Model

<div>Computer simulations of bio-molecular systems often use force fields, which are combinations of simple empirical atom-based functions to describe the molecular interactions. Even though polarizable force fields give a more detailed description of intermolecular interactions, nonpolarizable force fields, developed several decades ago, are often still preferred because of their reduced computation cost. Electrostatic interactions play a major role in bio-molecular systems and are therein described by atomic point charges.</div><div>In this work, we address the performance of different atomic charges to reproduce experimental hydration free energies in the FreeSolv database in combination with the GAFF force field. Atomic charges were calculated by two atoms-in-molecules approaches, Hirshfeld-I and Minimal Basis Iterative Stockholder (MBIS). To account for polarization effects, the charges were derived from the solute's electron density computed with an implicit solvent model and the energy required to polarize the solute was added to the free energy cycle. The calculated hydration free energies were analyzed with an error model, revealing systematic errors associated with specific functional groups or chemical elements. The best agreement with the experimental data is observed for the MBIS atomic charge method, including the solvent polarization, with a root mean square error of 2.0 kcal mol<sup>-1</sup> for the 613 organic molecules studied. The largest deviation was observed for phosphor-containing molecules and the molecules with amide, ester and amine functional groups.</div>

QUBEKit: Automating the Derivation of Force Field Parameters from Quantum Mechanics

2019 ◽  
Author(s):  
Joshua Horton ◽  
Alice Allen ◽  
Leela Dodda ◽  
Daniel Cole
Keyword(s):  
Quantum Mechanics ◽  
Force Field ◽  
Organic Molecules ◽  
Force Fields ◽  
Liquid Density ◽  
Small Organic Molecules ◽  
Automated Generation ◽  
Energy Of Hydration ◽  
Novel Method ◽  
Force Field Parameters

<div><div><div><p>Modern molecular mechanics force fields are widely used for modelling the dynamics and interactions of small organic molecules using libraries of transferable force field parameters. For molecules outside the training set, parameters may be missing or inaccurate, and in these cases, it may be preferable to derive molecule-specific parameters. Here we present an intuitive parameter derivation toolkit, QUBEKit (QUantum mechanical BEspoke Kit), which enables the automated generation of system-specific small molecule force field parameters directly from quantum mechanics. QUBEKit is written in python and combines the latest QM parameter derivation methodologies with a novel method for deriving the positions and charges of off-center virtual sites. As a proof of concept, we have re-derived a complete set of parameters for 109 small organic molecules, and assessed the accuracy by comparing computed liquid properties with experiment. QUBEKit gives highly competitive results when compared to standard transferable force fields, with mean unsigned errors of 0.024 g/cm3, 0.79 kcal/mol and 1.17 kcal/mol for the liquid density, heat of vaporization and free energy of hydration respectively. This indicates that the derived parameters are suitable for molecular modelling applications, including computer-aided drug design.</p></div></div></div>

QUBEKit: Automating the Derivation of Force Field Parameters from Quantum Mechanics

2019 ◽  
Author(s):  
Joshua Horton ◽  
Alice Allen ◽  
Leela Dodda ◽  
Daniel Cole
Keyword(s):  
Quantum Mechanics ◽  
Force Field ◽  
Organic Molecules ◽  
Force Fields ◽  
Liquid Density ◽  
Small Organic Molecules ◽  
Automated Generation ◽  
Energy Of Hydration ◽  
Novel Method ◽  
Force Field Parameters

<div><div><div><p>Modern molecular mechanics force fields are widely used for modelling the dynamics and interactions of small organic molecules using libraries of transferable force field parameters. For molecules outside the training set, parameters may be missing or inaccurate, and in these cases, it may be preferable to derive molecule-specific parameters. Here we present an intuitive parameter derivation toolkit, QUBEKit (QUantum mechanical BEspoke Kit), which enables the automated generation of system-specific small molecule force field parameters directly from quantum mechanics. QUBEKit is written in python and combines the latest QM parameter derivation methodologies with a novel method for deriving the positions and charges of off-center virtual sites. As a proof of concept, we have re-derived a complete set of parameters for 109 small organic molecules, and assessed the accuracy by comparing computed liquid properties with experiment. QUBEKit gives highly competitive results when compared to standard transferable force fields, with mean unsigned errors of 0.024 g/cm3, 0.79 kcal/mol and 1.17 kcal/mol for the liquid density, heat of vaporization and free energy of hydration respectively. This indicates that the derived parameters are suitable for molecular modelling applications, including computer-aided drug design.</p></div></div></div>

A Transferable, Polarisable Force Field for Ionic Liquids

2019 ◽  
Author(s):  
Kateryna Goloviznina ◽  
José N. Canongia Lopes ◽  
Margarida Costa Gomes ◽  
Agilio Padua
Keyword(s):  
Ionic Liquids ◽  
Force Field ◽  
Force Fields ◽  
Dipole Moments ◽  
Van Der Waals Interactions ◽  
First Principles Calculations ◽  
Ion Diffusion ◽  
Fixed Integer ◽  
Molecular Compounds ◽  
Induced Dipoles

A general, transferable polarisable force field for molecular simulation of ionic liquids and their mixtures with molecular compounds is developed. This polarisable model is derived from the widely used CL\&P fixed-charge force field that describes most families of ionic liquids, in a form compatible with OPLS-AA, one of the major force fields for organic compounds. Models for ionic liquids with fixed, integer ionic charges lead to pathologically slow dynamics, a problem that is corrected when polarisation effects are included explicitly. In the model proposed here, Drude induced dipoles are used with parameters determined from atomic polarisabilities. The CL\&P force field is modified upon inclusion of the Drude dipoles, to avoid double-counting of polarisation effects. This modification is based on first-principles calculations of the dispersion and induction contributions to the van der Waals interactions, using symmetry-adapted perturbation theory (SAPT) for a set of dimers composed of positive, negative and neutral fragments representative of a wide variety of ionic liquids. The fragment approach provides transferability, allowing the representation of a multitude of cation and anion families, including different functional groups, without need to re-parametrise. Because SAPT calculations are expensive an alternative predictive scheme was devised, requiring only molecular properties with a clear physical meaning, namely dipole moments and atomic polarisabilities. The new polarisable force field, CL\&Pol, describes a broad set set of ionic liquids and their mixtures with molecular compounds, and is validated by comparisons with experimental data on density, ion diffusion coefficients and viscosity. The approaches proposed here can also be applied to the conversion of other fixed-charged force fields into polarisable versions.<br>

scholarly journals Measurements of periodically perturbed dewetting force fields and their consequences on the symmetry of the resulting patterns

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Konstantinos Roumpos ◽  
Sarah Fontaine ◽  
Thomas Pfohl ◽  
Oswald Prucker ◽  
Jürgen Rühe ◽  
...  
Keyword(s):  
Force Field ◽  
Driving Force ◽  
Force Fields ◽  
Contact Lines ◽  
Polymer Flow ◽  
Circular Symmetry ◽  
Pillar Array ◽  
Restoring Forces ◽  
Micro Pillars ◽  
Circular Contact

AbstractWe studied the origin of breaking the symmetry for moving circular contact lines of dewetting polymer films suspended on a periodic array of pillars. There, dewetting force fields driving polymer flow were perturbed by elastic micro-pillars arranged in a regular square pattern. Elastic restoring forces of deformed pillars locally balance driving capillary forces and broke the circular symmetry of expanding dewetting holes. The observed envelope of the dewetting holes reflected the symmetry of the underlying pattern, even at sizes much larger than the characteristic period of the pillar array, demonstrating that periodic perturbations in a driving force field can establish a well-defined pattern of lower symmetry. For the presented system, we succeeded in squaring the circle.

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