Solvation Free Energy Calculations Research Articles

Studies on free energy calculations. II. A theoretical approach to molecular solvation

Using the concepts of scaled particle theory, an analytical theory is developed to investigate the limiting behavior of solvation free energies at the particle creation limit. The new theory directly incorporates the weakly attractive, dispersion interaction terms into the analytical calculations. For neutral molecular systems, the effects of longer ranged electrostatic interactions are also incorporated, albeit in an ad hoc way, and the validity of the utilized assumptions are then demonstrated with numerical examples. It is shown that it is possible to blend the numerical and analytical methods to increase the reliability of quantitative results, and, at the same time, to achieve savings on computational expenditure for certain types of calculations. Different methods of performing the thermodynamic integration in solvation free energy calculations are also compared. Studied examples clearly show the importance of proper treatment of the divergence at the particle creation limit in obtaining quantitatively reliable results for the solvation free energies.

Ab Initio Free Energy Perturbation Calculations of Solvation Free Energy Using the Frozen Density Functional Approach

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTAb Initio Free Energy Perturbation Calculations of Solvation Free Energy Using the Frozen Density Functional ApproachT. Wesolowski and A. WarshelCite this: J. Phys. Chem. 1994, 98, 20, 5183–5187Publication Date (Print):May 1, 1994Publication History Published online1 May 2002Published inissue 1 May 1994https://doi.org/10.1021/j100071a003RIGHTS & PERMISSIONSArticle Views485Altmetric-Citations143LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (2 MB) Get e-Alerts

Molecular simulation of alkyl boronic acids: Molecular mechanics and solvation free energy calculations

AbstractThe alkyl boronic acid moiety is incorporated into many biologically interesting structures. To provide parameters for molecular mechanics and dynamics studies of compounds containing this group, we performed ab initio calculations at the 6‐31G* level to obtain bond stretching, bending, and torsion constants. The hydrodynamic formulation of the time‐dependent density functional theory was used to calculate the attractive part of van der Waals (VDW) 6–12 potential. The geometry of boronic acid moiety of the 6‐31G* optimized methyl boronic acid was similar to that of the X‐ray crystal structure of phenyl boronic acid. To test the reliability of nonbonded parameters, Monte Carlo free energy perturbation simulations and the thermodynamic cycle approach were used to estimate the differences in solvation free energy between alkyl alcohol and alkyl boronic acid, both in water and in chloroform. These free energy differences were also obtained experimentally by measuring the vapor–water and water–chloroform partition coefficients. The close agreement between experimental values and the results of our simulations suggests the reliability of new molecular mechanics force‐field parameters for alkyl boronic acids. © 1994 by John Wiley & Sons, Inc.

Localization of bound water in the solution structure of a complex of the erythroid transcription factor GATA-1 with DNA.

The erythroid specific transcription factor GATA-1 is responsible for the regulation of transcription of erythroid-expressed genes and is an essential component required for the generation of the erythroid lineage. GATA-1 binds specifically as a monomer to the asymmetric consensus target sequence (T/A)GATA-(A/G) found in the cis-regulatory elements of all globin genes and most other erythroid specific genes that have been examined. We have previously determined the solution structure of the complex of the zinc-containing DNA-binding domain of chicken GATA-1 with its cognate DNA target site by multidimensional heteronuclear NMR. From previous studies of complexes between proteins and DNA, water appears to play an important role in DNA-protein recognition by mediating bridging hydrogen bonds between functional groups on the protein and DNA bases. Solvation free energy calculations, however, suggest that hydrophobic interactions should exclude water from parts of the GATA-1:DNA interface. Using water-selective two-dimensional heteronuclear magnetic resonance spectroscopy, we have identified the location of bound water molecules in the specific complex of chicken GATA-1 with DNA. A number of water molecules could be detected between the protein and the phosphate backbone, as well as at the solvent exposed surface of the protein. However, no water molecules could be observed at the interface of the protein with the bases of the DNA. With only one exception, the bound water molecules have a residency time > 200-300 ps. Unlike other protein-DNA complexes, the majority of specific interactions between GATA-1 and the DNA bases in the major groove are hydrophobic in nature. The exclusion of water from the protein-DNA base interface in the major groove supports the view that the specific binding energy is indeed dominated by hydrophobic effects.

Calculation of solvation free energies using a density functional/molecular dynamics coupled potential

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTCalculation of solvation free energies using a density functional/molecular dynamics coupled potentialRobert V. Stanton, David S. Hartsough, and Kenneth M. Merz Jr.Cite this: J. Phys. Chem. 1993, 97, 46, 11868–11870Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://doi.org/10.1021/j100148a005RIGHTS & PERMISSIONSArticle Views725Altmetric-Citations131LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (1 MB) Get e-Alerts

Polarization of the nucleic acid bases in aqueous solution

We present calculations of the absolute free energy of solvation of five nucleic acid bases and five methylated nucleic acid bases using a recently developed local-field SCF procedure in which the electronic structure and geometry are both optimized in the presence of solvent. The calculated solvation free energies are increased 23%–24% by the aqueous-phase relaxation.

Quantum-mechanical calculations of solvation free energies. A combined ab initio pseudopotential free-energy perturbation approach

A practical ab initio quantum-mechanical approach for calculations of free energies of molecules in solutions is developed. This approach treats the solute molecules by an explicit ab initio self-consistent-field approach while representing the solvent molecules by a pseudopotential. The solvation energies are evaluated by a free-energy perturbation approach that uses the distribution function associated with a classical force field as a reference state for the quantum-mechanical calculations. The performance of the method is examined by evaluating the solvation energy of an Li+ ion. It is found that the calculation times are not much longer than that of the corresponding classical free-energy perturbation calculations.

Continuum model calculations of solvation free energies: accurate evaluation of electrostatic contributions

The electrostatic contributions to free energies of solvation of several small molecules have been calculated, treating the solvent as a statistical continuum. The computational method is based on solving the linearized Poisson-Boltzmann equation for the electrostatic potentials using the finite-difference scheme. A careful study of convergence indicates the importance of a fine grid spacing, as well as the short comings of rotational averaging. The computed free energies of solvation are in excellent agreement with the experimental results as well as the free energy perturbation calculations

Quantum-chemical calculations of the hydration energies of organic cations and anions in the framework of a continuum solvent approximation

We investigate the method of calculation of solvation energies using the continuum solvent model and the semiemperical NDDO quantum-chemical background. The electrostatic part of the calculation is based on the Miertuš-Scrocco-Tomasi procedure treating the solvent as a dielectric continuum with a cavity and numerically solving the integral equation for the charge distribution on the cavity surface. Its efficiency was significantly increased by accelerating the convergence of the surface integration procedure and modifying the iterative scheme. The calculated solvation free energies of numerous organic ions agree with the experimental estimates within 2–3 kcal/mol. The specific solute-solvent interactions are shown to be important in several cases and a consistent procedure of calculating their contribution to the solvation energy is elaborated.

Prediction of a Crystallization Pathway for Z-DNA Hexanucleotides

Crystallization of macromolecules for structural studies has long been a hit-or-miss process. The crystallization of hexanucleotides as Z-DNA was studied, and it was shown that the cation concentration for crystal formation could be predicted from solvation free energy (SFE) calculations. Solution studies on the conformation and solubilities of the hexanucleotides showed that a critical concentration of the DNA in the Z-conformation must be present in solution to effect crystallization. The SFE calculations therefore predict the propensity of the hexanucleotides to adopt the left-handed conformation and the driving force required to reach this critical concentration relative to the intrinsic solubility of Z-DNA for crystallization.