Relative Binding Enthalpies from Molecular Dynamics Simulations Using a Direct Method.

ABSTRACT: The potential for reliably predicting relative binding enthalpies, ΔΔE, from a direct method utilizing molecular dynamics is examined for a system of three phosphotyrosyl peptides binding to a protein receptor, the Src SH2 domain. The binding enthalpies were calculated from the potential energy differences between the bound and the unbound end-states of each peptide from equilibrium simulations in explicit water. The statistical uncertainties in the ensemble-mean energy values from multiple, independent simulations were obtained using a bootstrap method. Simulations were initiated with different starting coordinates as well as different velocities. Statistical uncertainties in ΔΔE are 2 to 3 kcal/mol based on calculations from 40, 10 ns trajectories for each system (three SH2

SUBMITTER: Roy A 

PROVIDER: S-EPMC4095907 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature