Naslov
Molecular Mechanics - Poisson Boltzmann Surface Area calculations using AMBER program package - application to the human dipeptidyl petidase III

Autori
Tomić, Antonija ; Tomić, Sanja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Computational Electrostatics for Biological Applications - Book of Abstract / - , 2013, 39-39

Skup
Computational Electrostatics for Biological Applications (CEBA '13)

Mjesto i datum
Genova, Italija, 01.07.2013. - 03.07.2013

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
MM-PBSA; dipeptidyl petidase III; Amber

Sažetak
Molecular Mechanics - Poisson Boltzmann Surface Area (MM-PBSA)[1] is post-processing method implemented in AMBER program package, in which representative snapshots from an ensemble of conformations, generated by molecular dynamic (MD) or Monte Carlo simulations, are used to calculate the associated free energy value. Typically, binding free energy difference between bound and free state of a receptor and ligand are calculated. Binding free energy difference, or trend in the binding free energy difference is usually more important than their absolute free energy values. The enthalpic component of the free energy is calculated by combining the so-called gas phase energy contributions (internal (bond, angle and dihedral energies), van der Waales and electrostatic energies as calculated by MM force field and independent of the chosen solvent model) and the solvation free energy components (both polar and non-polar) calculated from an implicit solvent model for each system. The electrostatic portion is calculated using either Poisson Boltzmann (PB) or Generalized Born method. The PB equation is solved numerically by either the program pbsa[2-4] (previous MM-PBSA applications were mostly performed with a numerical PB solver in the widely used DelPhi program, implemented in AMBER program package) or by the Adaptive Poisson Boltzmann Solver (APBS) program through the iAPBS interface with AMBER. Estimation of the non-polar contribution to the solvation free energy is based on the solvent-accessible-surface-area calculations. Here, the results of MM-PBSA calculations, applied to study of free enzyme tertiary structure change[5] and enzyme-ligand binding will be presented. Structure used for MM- PBSA calculations were extracted from bound and unbound dipeptidyl peptidase III (DPP III) MD trajectories. The results agree very well with experimental findings that protein can adopt two different conformations, "open" and "closed". In addition, several ligand binding modes were found and binding with the ligand in an extended conformation, consistent with the experiment, was identified as the energetically most favorable one. In this conformation first two ligand residues form a β-strand which binds to the five- stranded β-core of DPP III in an antiparallel fashion.

Izvorni jezik
Engleski

Znanstvena područja
Kemija

POVEZANOST RADA