Quantum Effects in Cation Interactions with First and Second Coordination Shell Ligands in Metalloproteins

• DOI: 10.1021/acs.jctc.5b00524
• Publication Date: 2015-09-22T14:38:33Z
• Authors: Van Ngo; Mauricio C. da Silva; Maximilian Kubillus; Hui Li; Benoît Roux; Marcus Elstner; Qiang Cui; Dennis R. Salahub; Sergei Yu. Noskov
• Keywords: Partial charge; Electrostatics; Force Field; Intrinsically Disordered Proteins

Despite decades of investigations, the principal mechanisms responsible for high affinity and specificity proteins key physiological cations K+, Na+, Ca2+ remain a hotly debated topic. At core debate is an apparent need (or lack thereof) accurate description electrostatic response charge distribution in protein to binding ion. These effects range from partial electronic polarization directly ligating atoms long-range related transfer delocalization effects. While modeling cation recognition by metalloproteins warrants use quantum-mechanics (QM) calculations, most popular approximations used major biomolecular simulation packages rely on implicit That is, high-level QM computations ion are desirable, but they often unfeasible, because large size reactive-site models sample conformational space exhaustively at finite temperature. Several solutions this challenge have been proposed field, ranging recently developed Drude polarizable force-field simulations approximate tight-binding density functional theory (DFTB). To delineate usefulness different approximations, we examined accuracy three recent commonly theoretical numerical algorithms, namely, CHARMM C36, latest force fields, DFTB3 with 3OB parameters. We performed MD 30 cation-selective high-resolution X-ray structures create ensembles analysis levels theory, e.g., additive DFTB3, DFT. The results DFT were benchmark Drude, performance. explicit quantum unveils properties sites importance specific ion-protein interactions. One interesting findings that secondary coordination shells noticeably perturbed cation-dependent manner, showing significant upon Ca2+.