Each ligand was minimized while binding to its target protein using the in situ ligand minimization module with the following parameters: CHARMm as an input force field, minimization algorithm as smart minimizer, maximum minimization steps equal to 1000, minimization with RMS gradient equal to 0.001 Å, and minimization energy change set equal to zero.
For other test cases, the removal of this minimization step lead to less discriminative (as reflected by higher p-values), or even wrong predictions (data not shown).
The initial molecular conformations for the adducts were subjected to a constrained energy minimization step in order to remove steric clashes.
It is a common practice in FILTERSIM to group the identical patterns in several clusters prior to the distance minimization step.
Initial 3D model of the chimeras were submitted to an energy minimization step using the steepest descent algorithm [ 70].
The performance of initial structure of DSSP model achieved an average CA-RMSD of 2.78 Å, which reduced with energy minimization step (2.90 Å) and finally reached to 3.80 Å after performing 100 ps MD simulation (Additional file 2: Table S9−S11).
The iterative refinement procedure contains three main steps: (i) random sampling of the dihedral angles according to the biased probability Monte Carlo method (Abagyan and Totrov, 1994), (ii) a local minimization step, (iii) the Metropolis criterion (Metropolis et al., 1953) is then used to accept or reject a conformation.
A Morse oscillator model was used to represent covalent bonding in the conjugate gradients minimization step, while a harmonic oscillator approximation was utilized for the steepest descents protocol.
Furthermore, we also perform an energy minimization step of the entire pMHC structure to adjust the 'MHC donor' cleft to this new epitope followed by a second round of molecular docking.
Then the complexity of each minimization step is (O |B|^2)+O k|B|)), and the number of steps required is assumed to depend only on |B|.
