2.2 Protein preparation
PPI and PPepI dataset entries were imported in Schrödinger Maestro
[38] and prepared as discussed here. Each of the entries in both the
benchmarking dataset were prepared using a Protein Preparation Wizard
utility available in Maestro [38]. For each PDB, protein hydrogens
were stereochemically added and appropriate ionization states (at pH
7.0) for the acidic and basic amino acid residues were maintained.
Missing side-chain atoms were added using a rotamer library of Xiang and
Honig [41] and missing backbone atoms were fixed using a loop
modeling procedure implemented in Prime [38]. Subsequently, the
structure optimization, which utilizes maximization of hydrogen bonding,
was carried out to i) identify the most probable positions for freely
rotating –OH and –SH hydrogens, ii) to assign the correct protonation
states of charged residues, iii) tautomers of His, and iv) Chi ‘flip’ of
Asn, Gln and His residues. Finally, to relieve any steric clashes within
atoms, the structures were energy minimized using OPLS2005 force field
until the heavy-atom displacement converged to root mean square
deviation (RMSD) of 0.30 Å. Many entries were manually examined and
processed, where it was not possible to prepare using the default
option.