Weak Interactions in Protein Folding: Hydrophobic Free Energy, van der Waals Interactions, Peptide Hydrogen Bonds, and Peptide Solvation

Baldwin, Robert L.

doi:10.1002/9783527619498.ch6

Cited by 16 publications

(18 citation statements)

References 126 publications

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“…The 'hydrophobic effect' was introduced by Tanford in 1980 to describe this phenomenom. To help elucidate the contribution of hydrophobic interactions to protein stability, a number of studies have modelled the formation of the hydrophobic core of the protein as the transference of nonpolar side chains from water to a nonpolar environment [38,40]. By studying the ∆G water-nonpolar , the change in free energy when a solute is transferred from water to a nonpolar environment, for amino acids, or chemical derivative, hydrophobicity scales for the 20 naturally occurring amino acids have been determined [41][42][43][44].…”

Section: Protein Thermodynamic and Kinetic Stabilitymentioning

confidence: 99%

The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding

2016

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One of the most exciting developments in the field of biological physics in recent years is the ability to manipulate single molecules and probe their properties and function. Since its emergence over two decades ago, single molecule force spectroscopy has become a powerful tool to explore the response of biological molecules, including proteins, DNA, RNA and their complexes, to the application of an applied force. The force versus extension response of molecules can provide valuable insight into its mechanical stability, as well as details of the underlying energy landscape. In this review we will introduce the technique of single molecule force spectroscopy using the atomic force microscope (AFM), with particular focus on its application to study proteins. We will review the models which have been developed and employed to extract information from single molecule force spectroscopy experiments. Finally, we will end with a discussion of future directions in this field.

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Section: Protein Thermodynamic and Kinetic Stabilitymentioning

confidence: 99%

The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding

2016

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“…Electrostatic forces play a major role in biological processes, particularly in proteinligand binding [24][25][26][27][28]. Cramer and Truhlar's SMD solvent model [29,30] which included water-octanol partition transfer energies, and hydrogen bonding interaction in the parameterization and optimization of their model, is well suited for biological solvent modelling.…”

mentioning

confidence: 99%

Statins in therapy: Understanding their hydrophilicity, lipophilicity, binding to 3-hydroxy-3-methylglutaryl-CoA reductase, ability to cross the blood brain barrier and metabolic stability based on electrostatic molecular orbital studies

Fong¹

2014

European Journal of Medicinal Chemistry

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The atomic electrostatic potentials calculated by the CHELPG method have been shown to be sensitive indicators of the gas phase and solution properties of the statins. Solvation free energies in water, n-octanol and n-octane have been determined using the SMD solvent model. The percentage hydrophilicity and hydrophobicity (or lipophilicity) of the statins in solution have been determined using (a) the differences in solvation free energies between n-octanol and n-octane as a measure of hydrophilicity, and the solvation energy in octane as a measure of hydrophobicity (b) the sum of the atomic electrostatic charges on the hydrogen bonding and polar bonding nuclei of the common pharmacophore combined with a solvent measure of hydrophobicity, and (c) using the buried surface areas after statin binding to HMGCR to calculate the hydrophobicity of the bound statins. The data suggests that clinical definitions of statins as either "hydrophilic" or "lipophilic" based on experimental partition coefficients are misleading. An estimate of the binding energy between rosuvastatin and HMGCR has been made using: (a) a coulombic electrostatic interaction model, (b) the calculated desolvation and resolvation of the statin in water, and (c) the first shell transfer solvation energy as a proxy for the restructuring of the water molecules immediately adjacent to the active binding site of HMGCR prior to binding. Desolvation and resolvation of the statins before and after binding to HMGCR are major determinants of the energetics of the binding process. An analysis of the amphiphilic nature of lovastatin anion, acid and lactone and fluvastatin anion and their abilities to cross the blood brain barrier has indicated that this process may be dominated by desolvation and resolvation effects, rather than the statin molecular size or statin-lipid interactions within the bilayer. The ionization energy and electron affinity of the statins are sensitive physical indicators of the ease that the various statins can undergo endogenous oxidative metabolism. The absolute chemical hardness is also an indicator of the stability of the statins, and may be a useful indicator for drug design.

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“…6-10 within the protease environment. 18,19 It is also clear that hydrophobic interactions between the S1,S1 0 ,S2 and S2 0 protease sites and the hydrophobic regions of inhibitors is also an important factor. In the analysis below, DG solvation is considered to represent the inhibitor in the bulk water environment, the non-polar contribution to solvation, DG desol,CDS is considered to represent the solvation shell around the inhibitor as it binds to the enzyme, DG lipophilicity (the free energy of solvation in n-octane) represents the hydrophobic interaction between inhibitor and the enzyme, the dipole moment in water is taken to represent the polar interaction between the inhibitor and solvent and enzyme, and the molecular volume in water is taken to represent the molecular size of the solvated inhibitor.…”

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confidence: 98%

The effect of desolvation on the binding of inhibitors to HIV-1 protease and cyclin-dependent kinases: Causes of resistance

Fong¹

2016

Bioorganic & Medicinal Chemistry Letters

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Studies of the cyclin-dependent kinase inhibitors and HIV-1 protease inhibitors have confirmed that ligand-protein binding is dependent on desolvation effects. It has been found that a four parameter linear model incorporating desolvation energy, lipophilicity, dipole moment and molecular volume of the ligands is a good model to describe the binding between ligands and kinases or proteases. The resistance shown by MDR proteases to the anti-viral drugs is multi-faceted involving varying changes in desolvation, lipophilicity and dipole moment interaction compared to the non-resistant protease. Desolvation has been shown to be the dominant factor influencing the effect of inhibitors against the cyclin-dependent kinases, but lipophilicity and dipole moment are also significant factors. The model can differentiate between the inhibitory activity of CDK2/cycE, CDK1/cycB and CDK4/cycD enzymes.

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Weak Interactions in Protein Folding: Hydrophobic Free Energy, van der Waals Interactions, Peptide Hydrogen Bonds, and Peptide Solvation

Cited by 16 publications

References 126 publications

The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding

The physics of pulling polyproteins: a review of single molecule force spectroscopy using the AFM to study protein unfolding

Statins in therapy: Understanding their hydrophilicity, lipophilicity, binding to 3-hydroxy-3-methylglutaryl-CoA reductase, ability to cross the blood brain barrier and metabolic stability based on electrostatic molecular orbital studies

The effect of desolvation on the binding of inhibitors to HIV-1 protease and cyclin-dependent kinases: Causes of resistance

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