TY - JOUR

T1 - An assessment of water placement algorithms in quantum mechanics/molecular mechanics modeling

T2 - the case of rhodopsins' first spectral absorption band maxima

AU - Nikolaev, Dmitrii M.

AU - Shtyrov, Andrey A.

AU - Mereshchenko, Andrey S.

AU - Panov, Maxim S.

AU - Tveryanovich, Yuri S.

AU - Ryazantsev, Mikhail N.

N1 - Funding Information: The work was funded by the Russian Science Foundation (RSF), grant No. 20-13-00303. The authors acknowledge Resource Center ‘‘Computer Center of SPbU’’.

PY - 2020/8/28

Y1 - 2020/8/28

N2 - 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 (λmax) 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 λmax 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 λmax from the experimental λmax. Although the major effect of water molecules on λmax originates from the water molecules located in the binding pocket, the water molecules outside the binding pocket also affect the calculated λmax 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.

AB - 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 (λmax) 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 λmax 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 λmax from the experimental λmax. Although the major effect of water molecules on λmax originates from the water molecules located in the binding pocket, the water molecules outside the binding pocket also affect the calculated λmax 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.

KW - BINDING AFFINITIES

KW - STRUCTURAL-CHANGES

KW - VISUAL PIGMENTS

KW - PROTEIN

KW - MOLECULES

KW - BACTERIORHODOPSIN

KW - SHIFT

KW - LIGHT

KW - ACTIVATION

KW - HYDRATION

UR - http://www.scopus.com/inward/record.url?scp=85090068602&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/ca6ae855-49dd-3473-a2f0-6298b3c5865f/

U2 - 10.1039/d0cp02638g

DO - 10.1039/d0cp02638g

M3 - Article

C2 - 32761024

AN - SCOPUS:85090068602

VL - 22

SP - 18114

EP - 18123

JO - Physical Chemistry Chemical Physics

JF - Physical Chemistry Chemical Physics

SN - 1463-9076

IS - 32

ER -