About this Biochemistry, Genetics and Molecular Biology article

Is the prediction of p K ~a~ values by constant‐pH molecular dynamics being hindered by inherited problems? by Miguel Machuqueiro; António M. Baptista is a Biochemistry, Genetics and Molecular Biology article available to read on EtoBox.

## Abstract In this study, we investigate two factors that can hinder the performance of constant‐pH molecular dynamics methods in predicting protein p__K__~a~ values, using hen egg white lysozyme as a test system. The first factor is related to the molecular definition and p__K__~a~ value of model compounds in the Poisson‐Boltzmann framework. We address this by defining the model compound as a molecular fragment with an associated p__K__~a~ value that is calibrated against experimental data, which results in a decrease of 0.12 units in p__K__~a~ errors. The second addressed factor is the possibility that detrimental structural distortions are being introduced in the simulations by the underlying molecular mechanics force field. This issue is investigated by analyzing how the gradual structural rearrangements affect the predicted p__K__~a~ values. The two GROMOS force fields studied here (43A1 and 53A6) yield good p__K__~a~ predictions, although a time‐dependent performance is observed: 43A1 performs better after a few nanoseconds of structural reorganization (p__K__~a~ errors of ∼0.45), while 53A6 gives the best prediction right at the first nanosecond (p__K__~a~ errors of 0.42).

Author

Miguel Machuqueiro; António M. Baptista

Publisher

John Wiley and Sons; Wiley (John Wiley & Sons); Wiley-Liss Inc; Wiley (ISSN 0887-3585)

Published

2011

Language

EN

Field

Biochemistry, Genetics and Molecular Biology (Life Sciences)