Figure 1 | Scientific Reports

Figure 1

From: Rational Design of Highly Potent and Slow-Binding Cytochrome bc1 Inhibitor as Fungicide by Computational Substitution Optimization

Figure 1

Diagrammatic representation of the workflow of CSO.

The CSO protocol was designed to automatically perform computational substitution, energy minimization and binding affinity evaluation: (1) The MD simulation of protein with original “hit” ligand was performed. (2) In order to obtain a representative ensemble of the binding structures, snapshots were collected from the MD trajectory at regular intervals and minimized. (3) The “Hit” ligand in each snapshot collected from the MD trajectory was mutated to new ligand with substitutions using the library of substitution and minimized. Each substitution group was set to link with the specific site of “Hit” compounds. (4) ΔΔG was calculated and the final binding free energy change is the average of the calculated values associated with each snapshot. New leads were finally determined according to the order of the binding free-energy shifts.

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