Conformational Entropy of Biomolecules Thermodynamics from protein molecular dynamics Numata 2007英文电子书.pdf

Genome Informatics vol. 18 No. 1 /journal.html CONFORMATIONAL ENTROPY OF BIOMOLECULES: BEYOND THE QUASI-HARMONIC APPROXIMATION JORGE NUMATA1 MICHAEL WAN1, 2 numata@chemie.fu-berlin.de mwan@ ERNST-WALTER KNAPP1 knapp@chemie.fu-berlin.de 1 Macromolecular Modeling Group, Dept. of Chemistry and Biochemistry, Freie Universitaet Berlin, Takustr. 6, Berlin 14195 Germany 2 Aspuru -Guzik Research Group, Harvard University, Dept. of Chemistry and Chemical Biology, 12 Oxford Street, Cambridge, MA 02138, USA 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