The universal statistical distributions of the affinity, equilibrium constants, kinetics and specificity in biomolecular recognition.
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The results of the analytical studies are confirmed by the microscopic flexible docking simulations.Our study provides new insights into the statistical nature of thermodynamics, kinetics and function from different ligands binding with a specific receptor or equivalently specific ligand binding with different receptors.The elucidation of distributions of the kinetics and free energy has guiding roles in studying biomolecular recognition and function through small-molecule evolution and chemical genetics.
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PubMed Central - PubMed
Affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, ChangChun, Jilin, P.R. China.
ABSTRACT
We uncovered the universal statistical laws for the biomolecular recognition/binding process. We quantified the statistical energy landscapes for binding, from which we can characterize the distributions of the binding free energy (affinity), the equilibrium constants, the kinetics and the specificity by exploring the different ligands binding with a particular receptor. The results of the analytical studies are confirmed by the microscopic flexible docking simulations. The distribution of binding affinity is Gaussian around the mean and becomes exponential near the tail. The equilibrium constants of the binding follow a log-normal distribution around the mean and a power law distribution in the tail. The intrinsic specificity for biomolecular recognition measures the degree of discrimination of native versus non-native binding and the optimization of which becomes the maximization of the ratio of the free energy gap between the native state and the average of non-native states versus the roughness measured by the variance of the free energy landscape around its mean. The intrinsic specificity obeys a Gaussian distribution near the mean and an exponential distribution near the tail. Furthermore, the kinetics of binding follows a log-normal distribution near the mean and a power law distribution at the tail. Our study provides new insights into the statistical nature of thermodynamics, kinetics and function from different ligands binding with a specific receptor or equivalently specific ligand binding with different receptors. The elucidation of distributions of the kinetics and free energy has guiding roles in studying biomolecular recognition and function through small-molecule evolution and chemical genetics. No MeSH data available. Related in: MedlinePlus |
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Mentions: In Fig 6, we show the logarithm of the equilibrium constant distribution for the 720 small molecule binding with Cox2. We see that the logarithm of equilibrium constant can be fitted well with a normal distribution near the mean while near the tail can be fitted well with a exponential distribution. Thus, we can extrapolate the statistical properties of the equilibrium constant distribution. That is, the equilibrium constant can be fitted well with a log-normal distribution near the mean while near the tail can be fitted well with a power law distribution. In contrast to the gaussian distribution, the log-normal distribution has a longer tail representing the higher frequencies of equilibrium constant when plotted in the original scale without taking the logarithm. The power law distribution of the equilibrium constant suggests most of the equilibrium constants of the ligands with random sequence binding to the receptor are small and binding complex are less stable. The large equilibrium constants although rare can contribute greatly in determining the biological stable function. They are the critical ones in molecular recognition. |
View Article: PubMed Central - PubMed
Affiliation: State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, ChangChun, Jilin, P.R. China.
No MeSH data available.