I am calculating the oniom energy for a complex, receptor only and ligand only to calculate the free binding energy of the ligand of interest. I've seen different papers that do get similar kcal/mol calculations to their respective docking experiments but wanted an opinion on if it truly makes sense to do so. Both methods are taking in completely different things when forming their calculations. I figured each would only be able to be compared relative to each other? Example. Ligands can only be compared to each other via docking alone and ligands used in oniom can only be compared to each other through oniom.
Some factors to consider when comparing results from different methods:
1. Methodological differences: Docking and free energy calculations using ONIOM are based on different underlying principles and assumptions. Docking typically predicts the binding pose and affinity of a ligand to a receptor based on scoring functions and geometric complementarity. ONIOM calculations, on the other hand, use a combination of quantum mechanical (QM) and molecular mechanics (MM) methods to describe the electronic structure and energetics of a system. These differences in approach can lead to variations in the absolute values obtained.
2. Relative comparisons: As you correctly mentioned, the primary utility of comparing results from different methods lies in their relative comparisons. The goal is to assess the relative binding affinities or trends between different ligands or receptor-ligand complexes within the same method. For example, if docking experiments consistently rank a set of ligands in a certain order of affinity, and the ONIOM calculations show a similar trend, it provides confidence in the relative comparison between ligands using both methods.
3. Calibration and validation: To establish a meaningful correlation between different methods, it is often necessary to calibrate and validate the results against experimental data or reference datasets. This can involve benchmarking a set of compounds with known binding affinities and comparing the relative rankings obtained from different methods. Calibration can help adjust the scaling factors or parameters to improve the agreement between methods and experimental results.
4. Limitations and assumptions: It's important to consider the limitations and assumptions of each method. Docking, for instance, may not fully capture the precise energetics of the binding process, while ONIOM calculations may have limitations in terms of the chosen level of theory, basis set, or representation of the system. Understanding these limitations can guide the interpretation and comparison of results.
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