How Can Hydrophobic Association Be Enthalpy Driven?
نویسندگان
چکیده
Hydrophobic association is often recognized as being driven by favorable entropic contributions. Here, using explicit solvent molecular dynamics simulations we investigate binding in a model hydrophobic receptor-ligand system which appears, instead, to be driven by enthalpy and opposed by entropy. We use the temperature dependence of the potential of mean force to analyze the thermodynamic contributions along the association coordinate. Relating such contributions to the ongoing changes in system hydration allows us to demonstrate that the overall binding thermodynamics is determined by the expulsion of disorganized water from the receptor cavity. Our model study sheds light on the solvent-induced driving forces for receptor-ligand association of general, transferable relevance for biological systems with poorly hydrated binding sites.
منابع مشابه
Thermodynamics of the self-association of glucagon.
In water, glucagon exists in an equilibrium between a trimer in which more than half of the peptide groups are in an alpha-helical configuration and a monomer which has a random coil configuration with few alpha-helical residues. The thermodynamics of this self-association have been evaluated by studying the temperature- and concentration-dependence of the mean residue ellipticity at 220 nm. Th...
متن کاملThermodynamic investigation of the interaction between Mono-s-chloroTriazinyl MCT Reactive Dyes and cetylpyridinium chloride inaqueous solution
The interactions two synthetic triazinyl reactive dyes Mono-s-chloro Triazinyl reactive dyes DI and DII with the cationic surfactant N-hexadecyl pyridinium chloride CPC were studied using a conductometric method in 25, 30, 35, 40 and 45ºC. The equilibrium constants and other thermodynamic parameters for the ion pair formation were calculated on the basis of a theoretical model using the data ob...
متن کاملHigh-definition self-assemblies driven by the hydrophobic effect: synthesis and properties of a supramolecular nanocapsule.
High definition self-assemblies, those that possess order at the molecular level, are most commonly made from subunits possessing metals and metal coordination sites, or groups capable of partaking in hydrogen bonding. In other words, enthalpy is the driving force behind the free energy of assembly. The hydrophobic effect engenders the possibility of (nominally) relying not on enthalpy but entr...
متن کاملWater-Restructuring Mutations Can Reverse the Thermodynamic Signature of Ligand Binding to Human Carbonic Anhydrase.
This study uses mutants of human carbonic anhydrase (HCAII) to examine how changes in the organization of water within a binding pocket can alter the thermodynamics of protein-ligand association. Results from calorimetric, crystallographic, and theoretical analyses suggest that most mutations strengthen networks of water-mediated hydrogen bonds and reduce binding affinity by increasing the enth...
متن کاملBinding of Hydrophobic Guests in a Coordination Cage Cavity is Driven by Liberation of “High‐Energy” Water
The cavity of an M8 L12 cubic coordination cage can accommodate a cluster of ten water molecules in which the average number of hydrogen bonds per water molecule is 0.5 H-bonds less than it would be in the bulk solution. The presence of these "hydrogen-bond frustrated" or "high-energy" water molecules in the cavity results in the hydrophobic effect associated with guest binding being predominan...
متن کامل