Conformational entropy of biomolecules: beyond the quasi-harmonic approximation.
A method is presented to calculate thermodynamic conformational entropy of a biomolecule from molecular dynamics simulation. Principal component analysis (the quasi-harmonic approximation) provides the first decomposition of the correlations in particle motion. Entropy is calculated analytically as a sum of independent quantum harmonic oscillators. The largest classical eigenvalues tend to be more anharmonic and show statistical dependence beyond correlation. Their entropy is corrected using a numerical method from information theory: the k-nearest neighbor algorithm. The method calculates a tighter upper limit to entropy than the quasi-harmonic approximation and is likewise applicable to large solutes, such as peptides and proteins. Together with an estimate of solute enthalpy and solvent free energy from methods such as MMPB/SA, it can be used to calculate the free energy of protein folding as well as receptor-ligand binding constants.
Numata
Jorge
J
Dept. of Chemistry and Biochemistry, Freie Universitaet Berlin, Takustr. 6, Berlin 14195, Germany. numata@chemie.fu-berlin.de
Wan
Michael
M
Knapp
Ernst-Walter
EW
D019277:Entropy; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry*
D011506:Proteins