Hydration Free Energies Using Semiempirical Quantum Mechanical Hamiltonians and a Continuum Solvent Model with Multiple Atomic-Type Parameters

2011 ◽  
Vol 115 (24) ◽  
pp. 7896-7905 ◽  
Author(s):  
Victor M. Anisimov ◽  
Claudio N. Cavasotto
Keyword(s):  
Quantum Mechanical ◽  
Free Energies ◽  
Continuum Solvent Model ◽  
Solvent Model ◽  
Atomic Type

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>

scholarly journals Protein-ligand free energies of binding from full-protein DFT calculations: convergence and choice of exchange-correlation functional

2021 ◽  
Author(s):  
Lennart Gundelach ◽  
Christofer S Tautermann ◽  
Thomas Fox ◽  
Chris-Kriton Skylaris
Keyword(s):  
Drug Discovery ◽  
Ligand Binding ◽  
Dft Calculations ◽  
Quantum Mechanical ◽  
Free Energies ◽  
Ligand Interaction ◽  
Exchange Correlation ◽  
Ligand Free ◽  
Protein Ligand Interaction ◽  
Binding Free Energies

The accurate prediction of protein-ligand binding free energies with tractable computational methods has the potential to revolutionize drug discovery. Modeling the protein-ligand interaction at a quantum mechanical level, instead of...

scholarly journals Molecular simulations of lipid membrane partitioning and translocation by bacterial quorum sensing modulators

PLoS ONE ◽  
2021 ◽  
Vol 16 (2) ◽  
pp. e0246187
Author(s):  
Tianyi Jin ◽  
Samarthaben J. Patel ◽  
Reid C. Van Lehn
Keyword(s):  
Quorum Sensing ◽  
Lipid Bilayers ◽  
Lipid Membrane ◽  
Computational Cost ◽  
Md Simulations ◽  
Umbrella Sampling ◽  
Communication Process ◽  
Free Energies ◽  
Membrane Partitioning ◽  
Solvent Model

Quorum sensing (QS) is a bacterial communication process mediated by both native and non-native small-molecule quorum sensing modulators (QSMs), many of which have been synthesized to disrupt QS pathways. While structure-activity relationships have been developed to relate QSM structure to the activation or inhibition of QS receptors, less is known about the transport mechanisms that enable QSMs to cross the lipid membrane and access intracellular receptors. In this study, we used atomistic MD simulations and an implicit solvent model, called COSMOmic, to analyze the partitioning and translocation of QSMs across lipid bilayers. We performed umbrella sampling at atomistic resolution to calculate partitioning and translocation free energies for a set of naturally occurring QSMs, then used COSMOmic to screen the water-membrane partition and translocation free energies for 50 native and non-native QSMs that target LasR, one of the LuxR family of quorum-sensing receptors. This screening procedure revealed the influence of systematic changes to head and tail group structures on membrane partitioning and translocation free energies at a significantly reduced computational cost compared to atomistic MD simulations. Comparisons with previously determined QSM activities suggest that QSMs that are least likely to partition into the bilayer are also less active. This work thus demonstrates the ability of the computational protocol to interrogate QSM-bilayer interactions which may help guide the design of new QSMs with engineered membrane interactions.

Free energies of solvation with quantum mechanical interaction energies from classical mechanical simulations

1999 ◽  
Vol 110 (3) ◽  
pp. 1329-1337 ◽  
Author(s):  
Robert H. Wood ◽  
Eric M. Yezdimer ◽  
Shinichi Sakane ◽  
Jose A. Barriocanal ◽  
Douglas J. Doren
Keyword(s):  
Quantum Mechanical ◽  
Interaction Energies ◽  
Free Energies ◽  
Mechanical Interaction

Quantum mechanical based approaches for predicting pKa values of carboxylic acids: evaluating the performance of different strategies

RSC Advances ◽  
2016 ◽  
Vol 6 (113) ◽  
pp. 112057-112064 ◽  
Author(s):  
Aida Mariana Rebollar-Zepeda ◽  
Annia Galano
Keyword(s):  
Carboxylic Acids ◽  
Quantum Mechanical ◽  
Pka Values ◽  
Solvent Model

The FP method is recommended for estimating pKa values of carboxylic acids for which this information is still unknown, especially in combination with the PBE0 functional (MUE = 0.26) and the SMD solvent model.

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