Calcium ion binding to calmodulin: binding free energy calculation using the molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) method by incorporating implicit polarization

2020 ◽  
pp. 1-10
Author(s):  
Abdul Basit ◽  
Rakesh Kumar Mishra ◽  
Pradipta Bandyopadhyay
Keyword(s):  
Free Energy ◽  
Surface Area ◽  
Calcium Ion ◽  
Binding Free Energy ◽  
Free Energy Calculation ◽  
Ion Binding ◽  
Energy Calculation ◽  
Calmodulin Binding ◽  
Poisson Boltzmann ◽  
Calcium Ion Binding

Application of the ESMACS Binding Free Energy Protocol to a Highly Varied Ligand Dataset: Lactate Dehydogenase A

2019 ◽  
Author(s):  
David Wright ◽  
Fouad Husseini ◽  
Shunzhou Wan ◽  
Christophe Meyer ◽  
Herman Van Vlijmen ◽  
...  
Keyword(s):  
Free Energy ◽  
Surface Area ◽  
Binding Free Energy ◽  
Normal Mode Analysis ◽  
Binding Mode ◽  
Accessible Surface Area ◽  
Solvent Accessible Surface Area ◽  
Mode Analysis ◽  
Energy Calculation ◽  
Accessible Surface

<div>Here, we evaluate the performance of our range of ensemble simulation based binding free energy calculation protocols, called ESMACS (enhanced sampling of molecular dynamics with approximation of continuum solvent) for use in fragment based drug design scenarios. ESMACS is designed to generate reproducible binding affinity predictions from the widely used molecular mechanics Poisson-Boltzmann surface area (MMPBSA) approach. We study ligands designed to target two binding pockets in the lactate dehydogenase A target protein, which vary in size, charge and binding mode. When comparing to experimental results, we obtain excellent statistical rankings across this highly diverse set of ligands. In addition, we investigate three approaches to account for entropic contributions not captured by standard MMPBSA calculations: (1) normal mode analysis, (2) weighted solvent accessible surface area (WSAS) and (3) variational entropy. </div>

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