An assessment of water placement algorithms in quantum mechanics/molecular mechanics modeling: the case of rhodopsins' first spectral absorption band maxima

• Published in: Physical chemistry chemical physics : PCCP 2020-08, Vol.22 (32), p.18114-18123
• Main Authors: Nikolaev, Dmitrii M, Shtyrov, Andrey A, Mereshchenko, Andrey S, Panov, Maxim S, Tveryanovich, Yuri S, Ryazantsev, Mikhail N
• Format: Article
• Language: English
• Subjects: Absorption spectra; Algorithms; Bacteriorhodopsin; Binding; Chromophores; Holes; Hydration; Photosensitivity; Placement; Proteins; Quantum mechanics; Quantum physics; Water chemistry
• ISSN: 1463-9076; 1463-9084
• DOI: 10.1039/d0cp02638g

Quantum mechanics/molecular mechanics (QM/MM) models are a widely used tool to obtain detailed insight into the properties and functioning of proteins. The outcome of QM/MM studies heavily depends on the quality of the applied QM/MM model. Prediction and right placement of internal water molecules in protein cavities is one of the critical parts of any QM/MM model construction. Herein, we performed a systematic study of four protein hydration algorithms. We tested these algorithms for their ability to predict X-ray-resolved water molecules for a set of membrane photosensitive rhodopsin proteins, as well as the influence of the applied water placement algorithms on the QM/MM calculated absorption maxima ( λ max ) of these proteins. We used 49 rhodopsins and their intermediates with available X-ray structures as the test set. We found that a proper choice of hydration algorithms and setups is needed to predict functionally important water molecules in the chromophore-binding cavity of rhodopsins, such as the water cluster in the N-H region of bacteriorhodopsin or two water molecules in the binding pocket of bovine visual rhodopsin. The QM/MM calculated λ max of rhodopsins is also quite sensitive to the applied protein hydration protocols. The best methodology allows obtaining an 18.0 nm average value for the absolute deviation of the calculated λ max from the experimental λ max . Although the major effect of water molecules on λ max originates from the water molecules located in the binding pocket, the water molecules outside the binding pocket also affect the calculated λ max mainly by causing a reorganization of the protein structure. The results reported in this study can be used for the evaluation and further development of hydration methodologies, in general, and rhodopsin QM/MM models, in particular. Accurate prediction of water molecules in protein cavities is an important factor for obtaining high-quality rhodopsin QM/MM models.