Polar Solvation Energy and Entropy Calculation with MM/PB(GB)SA
Inquiry
Polar solvation energy and entropy are two essential parts in the binding energy. The polar solvation energy comes from the electrostatic interaction between the solute and the solvent molecules, and the implicit solvation energy is used in the calculation. In the solvent model, the solvent is regarded as a continuous medium, and the corresponding Poisson Boltzmann (PB) equation is linearized and solved numerically. The polar solvation term is originally obtained by solving the PB equation numerically. Nowadays, it can also be calculated by the Generalized Born (GB) approach (giving a MM/GBSA method), because such calculations sometimes are faster and pair-wise decomposable. Alfa Chemistry applies either PB equation or GB approach depending on the studied system. In terms of calculating the entropy, the contribution of the entropy of the gas phase is calculated according to the MM method in the MM-PBSA method. Moreover, our experts have apply a simple modification in MM/PB(GB)SA to obtain a more accurate result.
Figure 1. Total solvation free energy, surface, Lennard-Jones and electrostatic solvation energies for Barstar-Barnase at different separation distances. (Gravina, R. C.; et al. 2018)
Our Services
- At Alfa Chemistry, we mainly use the three-track scheme and the single-track scheme in MM-GBSA and MM-PBSA calculations.
- Several factors that can affect the calculation of MM/PB(GB)SA are optimized such as the length of the simulation time, the choice of force field, the dielectric constant of the solute, the solvent model, and the net charge of the system.
- In the case of unbalanced trajectories, the calculation of the PB part may become very slow, we therefore select a sufficiently balanced trajectory for calculation.
- Our teams can study different conformations of the receptor and the ligand in MD simulations and to calculate entropies from these, for example, from the dihedral distributions.
Polar Solvation Energy Calculation Process
- First, extract frames from a single or multiple complex molecular dynamics simulation which allows for the comparison between multiple trajectories.
- Second, the complex frames is split into the single components including complex, protein and ligand.
- Third, the polar solvation energy value is calculated using Poisson Boltzmann equation or generalized Born equation.
∆G_{polar} = ∆G_{PB}
Nonpolar Solvation Entropy Calculation Process
In addition to polar solvation energy calculation, Alfa Chemistry supports the entropy contribution calculation:
- First, minimize the energy (without truncation for non-bond interactions)
- We include all residues and water molecules within 12 Å of the ligand in the minimization, but fix the water molecules and residues between 8 and 12 Å in the minimization and ignore their contributions to the entropy.
- Second, perform normal analysis to calculate the mass-weighted Hessian matrix.
- Third, calculate the vibrational frequencies.
- Fourthly, perform diagonalization, and use the obtained frequency to calculate the entropy contribution.
Our Advantages
- We have proposed an improved method to solve the PB equation to increase the calculation speed.
- Our predictions of the polar solvation energies and entropy are in an excellent agreement with experimental data, which supports the validity of the proposed model.
- We also evaluate two variants of the three-dimensional reference site interaction model (3D-RISM) to give more accurate solvation energies.
Our polar solvation energy and entropy calculation with MM/PB(GB)SA services remarkably reduce the cost, promote further experiments, and accelerate the process of drug design for customers worldwide. Our personalized and all-around services will satisfy your innovative study demands. If you are interested in our services, please don't hesitate to contact us. We are glad to cooperate with you and witness your success!
Reference
- Gravina, R. C.; et al. Tailoring the Variational Implicit Solvent Method for New Challenges: Biomolecular Recognition and Assembly. Frontiers in Molecular Biosciences. 2018, 5: 13.