Some thermodynamic effects of varying nonpolar surfaces in protein-ligand interactions

The binding interactions of bovine serum albumin (BSA) with tetraphenylborate ions ([B(Ph)4]−) have been investigated by a set of experimental methods (isothermal titration calorimetry, steady-state fluorescence spectroscopy, differential scanning calorimetry and circular dichroism spectroscopy) and molecular dynamics-based computational approaches. Two sets of structurally distinctive binding sites in BSA were found under the experimental conditions (10 mM cacodylate buffer, pH 7, 298.15 K). The obtained results, supported by the competitive interactions experiments of SDS with [B(Ph)4]− for BSA, enabled us to find the potential binding sites in BSA. The first site is located in the subdomain I A of the protein and binds two [B(Ph)4]− ions (logK(ITC)1 = 7.09 ± 0.10; ΔG(ITC)1 = −9.67 ± 0.14 kcal mol−1; ΔH(ITC)1 = −3.14 ± 0.12 kcal mol−1; TΔS(ITC)1 = −6.53 kcal mol−1), whereas the second site is localized in the subdomain III A and binds five ions (logK(ITC)2 = 5.39 ± 0.06; ΔG(ITC)2 = −7.35 ± 0.09 kcal mol−1; ΔH(ITC)2 = 4.00 ± 0.14 kcal mol−1; TΔS(ITC)2 = 11.3 kcal mol−1). The formation of the {[B(Ph)4]−}–BSA complex results in an increase in the thermal stability of the alfa-helical content, correlating with the saturation of the particular BSA binding sites, thus hindering its thermal unfolding.

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Section: Isothermal Titration Calorimetry (Itc)mentioning

confidence: 99%

Effect of Tetraphenylborate on Physicochemical Properties of Bovine Serum Albumin

et al. 2021

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“…The crystal structures of the two proteins, PLpro (PDB ID - 7JRN) [62] and ADRP (PDB ID - 6WO2) [63] were downloaded from protein data bank (PDB). AutoDock 4.2 software [64] was used to perform all molecular docking calculations The crystal structures of the two proteins, PLpro (PDB ID - 7JRN) [62] (SARS-CoV-2 papain-like protease) and ADRP (PDB ID - 6WO2) [63] (SARS-CoV-2 ADP ribose phosphatase) were downloaded from protein data bank (PDB). The default protonation of ionizable residues in the proteins were set at pH 7.4 and polar hydrogens were added to the crystal structures of the proteins, prior to the docking process.…”

Section: Resultsmentioning

confidence: 99%

Exploring the structural, photophysical and optoelectronic properties of a diaryl heptanoid curcumin derivative and identification as a SARS-CoV-2 inhibitor

Archana

Armaković

et al. 2023

Journal of Molecular Structure

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“…Although enthalpy–entropy compensation (EEC) exists as an “X-factor,” which distinctly increases the challenges for compound optimization, to our knowledge there is currently no efficient way to avoid this effect . STRs show not only the changes of binding affinity but also the changes of thermodynamic parameters caused by small molecules . Therefore, the exploration of STRs is fundamentally important in medicinal chemistry, especially for the design of optimal small molecules.…”

Section: Thermodynamic-guided Small-molecule Optimizationmentioning

confidence: 99%

“…71 STRs show not only the changes of binding affinity but also the changes of thermodynamic parameters caused by small molecules. 72 Therefore, the exploration of STRs is fundamentally important in medicinal chemistry, especially for the design of optimal small molecules.…”

Section: Thermodynamic-guided Small-molecule Optimizationmentioning

confidence: 99%

Insight into Thermodynamic and Kinetic Profiles in Small-Molecule Optimization

et al. 2022

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Structure–activity relationships (SARs) and structure–property relationships (SPRs) have been considered the most important factors during the drug optimization process. For medicinal chemists, improvements in the potencies and druglike properties of small molecules are regarded as their major goals. Among them, the binding affinity and selectivity of small molecules on their targets are the most important indicators. In recent years, there has been growing interest in using thermodynamic and kinetic profiles to analyze ligand–receptor interactions, which could provide not only binding affinities but also detailed binding parameters for small-molecule optimization. In this perspective, we are trying to provide an insight into thermodynamic and kinetic profiles in small-molecule optimization. Through a highlight of strategies on the small-molecule optimization with specific cases, we aim to put forward the importance of structure–thermodynamic relationships (STRs) and structure–kinetic relationships (SKRs), which could provide more guidance to find safe and effective small-molecule drugs.

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Some thermodynamic effects of varying nonpolar surfaces in protein-ligand interactions

Cited by 7 publications

References 45 publications

Effect of Tetraphenylborate on Physicochemical Properties of Bovine Serum Albumin

Effect of Tetraphenylborate on Physicochemical Properties of Bovine Serum Albumin

Exploring the structural, photophysical and optoelectronic properties of a diaryl heptanoid curcumin derivative and identification as a SARS-CoV-2 inhibitor

Insight into Thermodynamic and Kinetic Profiles in Small-Molecule Optimization

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