Complex Based Pharmacophore are much better than Dynamics Based

Thanks Anum, Could you please send me the reference(s) regarding the same.

https://www.dovepress.com/structure-based-three-dimensional-pharmacophores-as-an-alternative-to--peer-reviewed-fulltext-article-JRLCR

Dear Anum,

Have gone through this article but, couldn't find the answer.

both the modeling techniques are useful but the limitations of Ligand based are more than the complex based as following

several key challenges in ligandbased pharmacophore modeling .

1. The first challenging problem is the modeling of ligand flexibility

2. Molecular alignment is the second challenging issue in ligandbased pharmacophore modeling

3. Another challenging problem lies in the practical task of proper selection of training set compounds

4. It may be possible that an active molecule cannot be identified if the conformation is missing

5. Different rotations might be very hard to be distinguished during the conformation generation 

etc. 

where as there is only one limitation of complex based pharmacophore modeling i-e 

1. too many chemical features can be identified for a specific binding site of the macromolecular target.  A pharmacophore model composed of too many

chemical features  is not suitable for practical applications, such as 3D database screening.

the solution to this problem is to  select a limited number of chemical features

 to construct a practical pharmacophore.  you can also overcome this signle issue by creating multicomplex-based comprehensive map and most-frequent pharmacophore model

Thanks dear for your sincere efforts but, the question asked is miles apart.

Dear Mohsin,

As per my level of understanding, both methods are optimal and its difficult to decide which one is better, in general. As both have their pros and cons.   

Using complex based method, ambiguities regarding the overall functional features of complex can be avoided as most of the features (interacting atom types and their positions) will be taken into account. However, with the Dynamics based, flexibility and structural rigidity of the complex will be considered.   

I think it depend on the type of protein-ligand complex (you want to model), that subsequently will decide the excellency of the method.  

Hope this will help !!

regards

athar

Hi

For pharmacophore model development, I would prefer multiple-complex based method using the PHASE module in Schrodinger's software:

Here is the link:

https://www.researchgate.net/publication/312187591_Mechanistic_Insights_into_the_Binding_of_Class_IIa_HDAC_Inhibitors_toward_Spinocerebellar_Ataxia_Type-2_A_3D-QSAR_and_Pharmacophore_Modeling_Approach

Article Mechanistic Insights into the Binding of Class IIa HDAC Inhi...

Dear Siddharth Sinha,

I didn't find any relevance of the suggested reference with the query. Could you please help me to understand the same.  

Dear Mohsin

Developing a Pharmacophore model using MD simulation studies involves the selection of representative structures from the highly clustered conformations of MD simulation trajectory to be used in the development of pharmacophore models.

But in this case also the methodology for the formation of pharmacophore is same as given in the manuscript in my last reply.