Solvation Free Energy of Biomacromolecules:  Parameters for a Modified Generalized Born Model Consistent with the AMBER Force Field

1998 ◽  
Vol 102 (47) ◽  
pp. 9571-9576 ◽  
Author(s):  
B. Jayaram ◽  
D. Sprous ◽  
D. L. Beveridge
Keyword(s):  
Free Energy ◽  
Force Field ◽  
Solvation Free Energy ◽  
Generalized Born ◽  
Amber Force Field ◽  
Born Model ◽  
Generalized Born Model

Free Energies of Hydration from a Generalized Born Model and an All-Atom Force Field

2004 ◽  
Vol 108 (41) ◽  
pp. 16264-16270 ◽  
Author(s):  
William L. Jorgensen ◽  
Jakob P. Ulmschneider ◽  
Julian Tirado-Rives
Keyword(s):  
Force Field ◽  
Free Energies ◽  
Generalized Born ◽  
Born Model ◽  
Generalized Born Model

scholarly journals GAFF/IPolQ-Mod+LJ-Fit: Optimized force field parameters for solvation free energy predictions

ADMET & DMPK ◽  
2020 ◽  
Author(s):  
Andreas Mecklenfeld ◽  
Gabriele Raabe
Keyword(s):  
Free Energy ◽  
Force Field ◽  
Fluid Phase ◽  
Solvation Free Energy ◽  
Rational Drug Design ◽  
Phase Behaviour ◽  
Liquid Density ◽  
Free Energies ◽  
Implicit Representation ◽  
Amber Force Field

<p class="ADMETabstracttext">Rational drug design featuring explicit solubility considerations can greatly benefit from molecular dynamics simulations, as they allow for the prediction of the Gibbs free energy of solvation and thus relative solubilities. In our previous work (A. Mecklenfeld, G. Raabe. J. Chem. Theory Comput. <strong>13 </strong>no. 12 (2017) 6266–6274), we have compared solvation free energy results obtained with the General Amber Force Field (GAFF) and its default restrained electrostatic potential (RESP) partial charges to those obtained by modified implicitly polarized charges (IPolQ-Mod) for an implicit representation of impactful polarization effects. In this work, we have adapted Lennard-Jones parameters for GAFF atom types in combination with IPolQ-Mod to further improve the accuracies of solvation free energy and liquid density predictions. We thereby focus on prominent atom types in common drugs. For the refitting, 357 respectively 384 systems were considered for free energies and densities and validation was performed for 142 free energies and 100 densities of binary mixtures. By the in-depth comparison of simulation results for default GAFF, GAFF with IPolQ-Mod and our new set of parameters, which we label GAFF/IPolQ-Mod+LJ-Fit, we can clearly highlight the improvements of our new model for the description of both relative solubilities and fluid phase behaviour.</p>

scholarly journals MMGB/SA Consensus Estimate of the Binding Free Energy Between the Novel Coronavirus Spike Protein to the Human ACE2 Receptor

2020 ◽  
Author(s):  
Negin Forouzesh ◽  
Alexey V. Onufriev
Keyword(s):  
Free Energy ◽  
Binding Free Energy ◽  
Quantitative Agreement ◽  
The Novel ◽  
Computationally Efficient ◽  
Generalized Born ◽  
Born Model ◽  
Generalized Born Model ◽  
Novel Coronavirus ◽  
Atomic Radii

AbstractThe ability to estimate protein-protein binding free energy in a computationally efficient via a physics-based approach is beneficial to research focused on the mechanism of viruses binding to their target proteins. Implicit solvation methodology may be particularly useful in the early stages of such research, as it can offer valuable insights into the binding process, quickly. Here we evaluate the potential of the related molecular mechanics generalized Born surface area (MMGB/SA) approach to estimate the binding free energy ΔGbind between the SARS-CoV-2 spike receptor-binding domain and the human ACE2 receptor. The calculations are based on a recent flavor of the generalized Born model, GBNSR6. Two estimates of ΔGbind are performed: one based on standard bondi radii, and the other based on a newly developed set of atomic radii (OPT1), optimized specifically for protein-ligand binding. We take the average of the resulting two ΔGbind values as the consensus estimate. For the well-studied Ras-Raf protein-protein complex, which has similar binding free energy to that of the SARS-CoV-2/ACE2 complex, the consensus ΔGbind = −11.8 ± 1 kcal/mol, vs. experimental −9.7 ± 0.2 kcal/mol.The consensus estimates for the SARS-CoV-2/ACE2 complex is ΔGbind = −9.4 ± 1.5 kcal/mol, which is in near quantitative agreement with experiment (−10.6 kcal/mol). The availability of a conceptually simple MMGB/SA-based protocol for analysis of the SARS-CoV-2 /ACE2 binding may be beneficial in light of the need to move forward fast.

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