Predicting protein-ligand binding affinity and correcting crystal structures with quantum mechanical calculations: lactate dehydrogenase A.

ABSTRACT: Accurately computing the geometry and energy of host-guest and protein-ligand interactions requires a physically accurate description of the forces in action. Quantum mechanics can provide this accuracy but the calculations can require a prohibitive quantity of computational resources. The size of the calculations can be reduced by including only the atoms of the receptor that are in close proximity to the ligand. We show that when combined with log P values for the ligand (which can be computed easily) this approach can significantly improve the agreement between computed and measured binding energies. When the approach is applied to lactate dehydrogenase A, it can make quantitative predictions about conformational, tautomeric and protonation state preferences as well as stereoselectivity

SUBMITTER: Lukac I 

PROVIDER: S-EPMC6388092 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature