Multi-Body Interactions in Molecular Docking Program Devised with Key Water Molecules in Protein Binding Sites

Abstract

Water molecules play an important role in modeling protein-ligand interactions. However, traditional molecular docking methods often ignore the impact of the water molecules by removing them without any analysis or keeping them as a static part of the proteins or the ligands. Hence, the accuracy of the docking simulations will inevitably be damaged. Here, we introduce a multi-body docking program which incorporates the fixed or the variable number of the key water molecules in protein-ligand docking simulations. The program employed NSGA II, a multi-objective optimization algorithm, to identify the binding poses of the ligand and the key water molecules for a protein. To this end, a force-field-based hydration-specific scoring function was designed to favor estimate the binding affinity considering the key water molecules. The program was evaluated in aspects of the docking accuracy, cross-docking accuracy, and screening efficiency. When the numbers of the key water molecules were treated as fixed-length optimization variables, the docking accuracy of the multi-body docking program achieved a success rate of 80.58% for the best RMSD values for the recruit of the ligands smaller than 2.0 Å. The cross-docking accuracy was investigated on the presence and absence of the key water molecules by four protein targets. The screening efficiency was assessed against those protein targets. Results indicated that the proposed multi-body docking program was with good performance compared with the other programs. On the other side, when the numbers of the key water molecules were treated as variable-length optimization variables, the program obtained comparative performance under the same three evaluation criterions. These results indicated that the multi-body docking with the variable numbers of the water molecules was also efficient. Above all, the multi-body docking program developed in this study was capable of dealing with the problem of the water molecules that explicitly participating in protein-ligand binding.

Bioinformatic Analysis of Antiviral Medicinal Compounds Against Sars Cov-2 Proteases

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Immunomodulatory potential of bioactive compounds of betel leaf extract targeting COVID-19 immunological human host proteins: An in silico study

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Molecular Docking Studies of Compounds from Brucea javanica (L.) Merr. Towards The Discovery of Potential H5N1 Neuraminidase Inhibitors

“…RMSD value is applied as a condition to evaluate the validity of the control docking process in which a control docking would be successful if RMSD obtained is no more than 2 Å. 19 Control docking result demonstrated that the RMSD value observed was 1.32 Å which means that the docking parameters set up were acceptable and therefore could be employed for virtual screening experiments upon compounds from B. javanica. The results (Table 1) showed that the free energy of binding of the compounds varies from -9.10 kcal/mol to -5.81 kcal/ mol.…”