Molecular electrostatics and pKa shifts calculations with the Generalized Born model. A tutorial through examples with Bluues2

Biomolecular electrostatics is of key importance for biological function and recognition. The continuum electrostatic model based on the Poisson-Boltzmann (PB) equation has been widely used to study biomolecular electrostatics. The solution of the PB equation gives the electrostatic potential over the space enclosing the molecule(s) of interest, typically obtained at points of a suitable grid. The Generalized Born (GB) model has been used to provide a useful approximation to the solution obtained by solving numerically the PB equation. The main advantage of the GB approach is to express the electrostatic energy of the system as the sum of pairwise interactions. The latter depend on geometric parameters (the GB radii) which depend on all atoms, and their radii, of the system. In this work we present a tutorial through examples for a more efficient and general version of the program Bluues which is able to compute: 1) the generalized Born radius of each atom; 2) the electrostatic potential at the surface of the molecule mapped to solvent accessible atoms; 3) the solvent accessible surface in a PDB formatted file; 4) the electrostatic potential in the volume surrounding the molecule; 5) the electrostatic free energy and different contributions to it; 6) the pH-dependent properties of proteins (total charge and pH-dependent free energy of folding) in the pH range −4 to 18; 7) the pKa shifts due to molecular structure of all ionizable groups. Program summary: Program Title: bluues2 CPC Library link to program files: https://doi.org/10.17632/bx98gcrzbg.1 Developer's repository link: https://github.com/federico-fogolari/bluues2 Code Ocean capsule: https://codeocean.com/capsule/9338710 Licensing provisions: GPLv3 Programming language: C Nature of problem: Biomolecular electrostatics is of key importance for biological function and recognition. Computation of electrostatic effects and their dissection in atomic contributions is a general problem in molecular modeling. Solution method: The GBR6 version of the Generalized Born (GB) model is implemented through surface integrals and all common molecular electrostatic analyses are performed by a single command line program. Additional comments including restrictions and unusual features: The program requires, as input, files in pqr format, which may be generated by independent software (e.g. babel, pdb2pqr). For the optional generation of the solvent excluded surface, the software msms must be installed and present in the path.