Two types of protein salt bridges studied by quantum calculation.

摘要

Two types of protein salt bridges in an aqueous environment, the arginine-acid salt bridge and the lysine-acid salt bridge, are studied here. The former is modeled by propionic acid and ethylguanidine, the latter by propionic acid and propyl amine. Both have been investigated by quantum calculations for the purpose of obtaining improved salt bridge potentials in an aqueous environment with constraints on the distances between the two functional groups, which are defined as the bridge lengths in this report, designed for applications to molecular dynamics simulations of ion channels. For the arginine-acid salt bridge, we perform optimization calculations on 13 molecular clusters corresponding to the salt bridge with 0 to 12 water molecules. For the lysine-acid salt bridge, we perform optimization calculations on 2 molecular clusters for the salt bridge with 0 or 1 water molecule. To each of the model systems, after obtaining its optimized geometry, we slowly vary the bridge lengths and bridge angles in three dimensions, and subsequently we perform COSMO, frequency and NBO calculations on the contracted and expanded model systems. COSMO calculations give the dielectric constant dependence, and the frequency provides the thermodynamic properties of the system while the NBO provides the electronic distributions and bonding information. We found: (1) there is a fill-in mechanism for water molecules to enter into the salt bridge systems; such a fill-in order may have periodicity in energy, as a function of number of water molecules. (2) we show that the salt bridge systems have both hydrophilic and hydrophobic properties; (3) we look into the proton ionization process from several new aspects in terms of comparison between potentials in two different salt bridge systems and the rates of Wiberg bond order change; (4) we have an in-depth look at effects that can cause large variations to system potentials, and we take note of effects that resulted from environments of limited amounts of local waters and that may have been missed by classical treatments; (5) we look into a new aspect in the applications of Wiberg bond order that are closely associated with the electron density in predicting the formation and disruption of bonding in the systems; (6) in regard to applications to simulations of ion channels, we discuss a possible method to formulate system potentials in specific environments.