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

Binding of calcium ion to calcium-binding proteins (CBP) triggers a large number of biological processes in a cell. CBP are known to play important roles in various diseases, such as cancer, alzheimer, and neuronal problems. However, the calculation of the binding affinity of calcium ion to CBP still possesses a significant challenge to the computational investigators. One of the main reasons for this difficulty is the polarization of CBP due to the binding of calcium. In the current work, we have used the implicit polarization method of Leontyev et al. (PCCP, 13.7 (2011): 2613-2626) to calculate the binding free energy of calcium ion binding to calmodulin, an important CBP. We have used the widely used MM-PBSA method to find a good protocol of calculation with implicit polarization. We have also optimized the best value of the calcium radius to match the experimental results. Our results show incorporation of polarization improves the agreement between the calculated and experimental results, although still, some discrepancy remains. On the whole, this work shows implicit polarization when combined with the MM-PBSA method can give results better than calculation without any polarization, and further improvement is necessary to get a quantitative match with experiments. Communicated by Ramaswamy H. Sarma

Automated summary

Binding of calcium ion to calcium-binding proteins triggers various biological processes, but calculating the binding affinity remains challenging. Implicit polarization method improves agreement between calculated and experimental results, indicating further improvement is necessary for quantitative match.