Hello!
Can anyone give a brief explanation about the relationship between ligand size (specifically, ligands smaller than 200 MW) and binding affinity in the in silico docking?
With the increasing of MW, can there be more false positives?
Really appreciate if you can give an idea about above matter or suggest a paper that deals with above issue...
ligand would be a lead compound when it fits the Lipinski rule of five..
Lipinski's rule states that, in general, an orally active drug has no more than one violation of the following criteria:
No more than 5 hydrogen bond donors (the total number of nitrogen–hydrogen and oxygen-hydrogen bonds)
No more than 10 hydrogen bond acceptors (all nitrogen or oxygen atoms)
A molecular mass of less than 500 daltons
A calculated octanol-water partition coefficient (Clog P) that does not exceed 5
better to google it.. but there is no connection between molecular weight and binding affinity...
So far, I have found no direct connection between molecular weight and binding affinity (from google at least).
Regarding the increasement of MW and binding affinity, when MW of a structure increases, that mostly because more substituents are added into the structure, which will affect the binding affinity. However, this effect can be positive or negative or sometimes in the middle as the added substituents might introduce new interaction (favorable, non-favorable, or maybe spacial obstructions).
=> Thus, in conclusion, yes, there are chances that increasing MW of a compound (by adding more substituents) on it would lead to better binding affinity. However, this does not mean the increasement of MW will lead to the increasement of fail positives as the increasement of MW would also lead to more complex substances that could well fit with the binding site (thus having better score and can be true positive).
Despite so, a study on the correlation between structure complexity and the method accuracy could be interesting.
As for the fail positive rate of molecular docking, it mostly due to the limitation of the scoring function, which purposely prioritize screening speed over accuracy.
The relationship between ligand size and binding affinity in silico docking can be complex and depends on several factors. In general, larger ligands are more likely to interact favorably with the binding site due to the greater contact area and flexibility. However, the size of the binder can also lead to steric challenges and difficulty in fitting. Binding affinity depends not only on size, but also on the chemical composition and properties of the ligand. Each system must be analyzed individually, considering other factors, such as physical-chemical properties and characteristics of the binding site.
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