Rationalization of the pK(a) Values of Alcohols and Thiols Using Atomic Charge Descriptors and Its Application to the Prediction of Amino Acid pK(a)'s

Date

2014-08-01

Author

Ugur, Ilke
Marıon, Antoıne
Parant, Stephane
Jensen, Jan H.
Monard, Gerald

Metadata

Show full item record

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

Item Usage Stats

12
views

0
downloads

In a first step toward the development of an efficient and accurate protocol to estimate amino acids' pK(a)'s in proteins, we present in this work how to reproduce the pK(a)'s of alcohol and thiol based residues (namely tyrosine, serine, and cysteine) in aqueous solution from the knowledge of the experimental pK(a)'s of phenols, alcohols, and thiols. Our protocol is based on the linear relationship between computed atomic charges of the anionic form of the molecules (being either phenolates, alkoxides, or thiolates) and their respective experimental pK(a) values. It is tested with different environment approaches (gas phase or continuum solvent-based approaches), with five distinct atomic charge models (Mulliken, Lowdin, NPA, Merz-Kollman, and CHelpG), and with nine different DFT functionals combined with 16 different basis sets. Moreover, the capability of semiempirical methods (AM1, RM1, PM3, and PM6) to also predict pK(a)'s of thiols, phenols, and alcohols is analyzed. From our benchmarks, the best combination to reproduce experimental pK(a)'s is to compute NPA atomic charge using the CPCM model at the B3LYP/3-21G and M062X/6-311G levels for alcohols (R-2 = 0.995) and thiols (R-2 = 0.986), respectively. The applicability of the suggested protocol is tested with tyrosine and cysteine amino acids, and precise pK(a) predictions are obtained. The stability of the amino acid pK(a)'s with respect to geometrical changes is also tested by MM-MD and DFT-MD calculations. Considering its strong accuracy and its high computational efficiency, these pK(a) prediction calculations using atomic charges indicate a promising method for predicting amino acids' pK(a) in a protein environment.

Subject Keywords

Molecular-dynamics simulations, Principles-based method, Substituted phenols, Ionizable groups, Dissociation-constants, Pk values, Semiempirical methods, Ionization-constants, Density functionals, Population analysis

URI

https://hdl.handle.net/11511/32990

Journal

JOURNAL OF CHEMICAL INFORMATION AND MODELING

DOI

https://doi.org/10.1021/ci500079w

Collections

Department of Chemistry, Article

Suggestions

OpenMETU
Core

Distance-based Indexing of Residue Contacts for Protein Structure Retrieval and Alignment Sacan, Ahmet; Toroslu, İsmail Hakkı; Ferhatosmanoglu, Hakan (2008-10-10) New protein structures are continuously being determined with the hope of deriving insights into the function and mechanisms of proteins, and consequently, protein structure repositories are growing by leaps and bounds. However, we are still far from having the right methods for sensitive and effective use of the available structural data. The fact that current structural analysis tools are impractical for large-scale applications have given rise to several approaches that try to quickly identify candidate ...
Learning functional properties of proteins with language models Unsal, Serbulent; Atas, Heval; ALBAYRAK, MUAMMER; TURHAN, KEMAL; Acar, Aybar Can; DOĞAN, TUNCA (2022-03-01) Data-centric approaches have been used to develop predictive methods for elucidating uncharacterized properties of proteins; however, studies indicate that these methods should be further improved to effectively solve critical problems in biomedicine and biotechnology, which can be achieved by better representing the data at hand. Novel data representation approaches mostly take inspiration from language models that have yielded ground-breaking improvements in natural language processing. Lately, these appr...
EXACTLY SOLVABLE EFFECTIVE MASS D-DIMENSIONAL SCHRODINGER EQUATION FOR PSEUDOHARMONIC AND MODIFIED KRATZER PROBLEMS IKHDAİR, SAMEER; Sever, Ramazan (World Scientific Pub Co Pte Lt, 2009-03-01) The point canonical transformation (PCT) approach is used to solve the Schrodinger equation for an arbitrary dimension D with a power-law position-dependent effective mass (PDEM) distribution function for the pseudoharmonic and modified Kratzer (Mie-type) diatomic molecular potentials. In mapping the transformed exactly solvable D-dimensional (D >= 2) Schrodinger equation with constant mass into the effective mass equation by using a proper transformation, the exact bound state solutions including the energ...
Speciation and determination of thiols in biological samples using high performance liquid chromatography-inductively coupled plasma-mass spectrometry and high performance liquid chromatography-Orbitrap MS Bakirdere, Sezgin; Bramanti, Emilia; D'ulivo, Alessandro; Ataman, Osman Yavuz; Mester, Zoltan (2010-11-08) An analytical method was developed for the determination of thiols in biological samples. Reverse phase chromatography coupled to ICP quaduropole MS or Orbitrap MS was employed for the separation and detection of thiols. For the determination of total thiols, oxidized thiols were reduced using dithiothreitol (DTT). Reduction efficiencies for species of interest were found to be close to 100%. Reduced thiols were derivatized by p-hydroxymercuribenzoate (PHMB) and then separated on a C8 column. Optimization o...
Site Specific Relationship for Strain Dependent Shear Modulus and Damping Using In Situ V S and High Strain Cyclic Test Results Zehtab, Kaveh Hassan; Yılmaz, Mustafa Tolga (2016-08-18) This study suggests a practical method for estimating site-specific strain dependent shear modulus and damping. The method uses in-situ shear wave velocity measurements and commercial cyclic laboratory tests on higher strains (i.e., 0.5% to 1%) in which the effect of disturbance is less significant. Shear modulus calculated using in-situ shear wave velocity and at higher cyclic shear strain, is used for building a hyperbolic relationship for shear stress and strain. Modified Masing's rule and the experiment...

Citation Formats

I. Ugur, A. Marıon, S. Parant, J. H. Jensen, and G. Monard, “Rationalization of the pK(a) Values of Alcohols and Thiols Using Atomic Charge Descriptors and Its Application to the Prediction of Amino Acid pK(a)’s,” JOURNAL OF CHEMICAL INFORMATION AND MODELING, pp. 2200–2213, 2014, Accessed: 00, 2020. [Online]. Available: https://hdl.handle.net/11511/32990.