A voltage-dependent fluorescent indicator for optogenetic applications, archaerhodopsin-3: Structure and optical properties from in silico modeling

Nikolaev, Dmitrii M.; Anton, Emil; Бойцов, В. М.; Panov, Maxim S.; Ryazantsev, Mikhail N.

doi:10.12688/f1000research.10541.1

Cited by 6 publications

(4 citation statements)

References 31 publications

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“…Also, as it was demonstrated in our recent work, 65 an advantage of I-TASSER models was detected when the structure of a archaerhodopsin 3, was predicted. While Medeller predicted seven TM helices and a long tail at the end of the seventh helix, I-TASSER predicted a half helix and a short tail instead.…”

Section: Results and Discussionsupporting

confidence: 69%

“…Because the retinal-binding pockets share very similar In other words, even though the conformation of several amino acid side-chains surrounding the chromophore was wrong in the predicted models, the subsequent insertion of retinal and geometry optimization corrected most problems (Figure 6). Also, as it was demonstrated in our recent work, 65 an advantage of I-TASSER models was detected when the structure of a archaerhodopsin 3, was predicted. While Medeller predicted seven TM helices and a long tail at the end of the seventh helix, I-TASSER predicted a half helix and a short tail instead.…”

Section: ■ Methodssupporting

confidence: 69%

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A Comparative Study of Modern Homology Modeling Algorithms for Rhodopsin Structure Prediction

et al. 2018

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Rhodopsins are seven α-helical membrane proteins that are of great importance in chemistry, biology, and modern biotechnology. Any in silico study on rhodopsin properties and functioning requires a high-quality three-dimensional structure. Due to particular difficulties with obtaining membrane protein structures from the experiment, in silico prediction of the three-dimensional rhodopsin structure based only on its primary sequence is an especially important task. For the last few years, significant progress was made in the field of protein structure prediction, especially for methods based on comparative modeling. However, the majority of this progress was made for soluble proteins and further investigations are needed to achieve similar progress for membrane proteins. In this paper, we evaluate the performance of modern protein structure prediction methodologies (implemented in the Medeller, I-TASSER, and Rosetta packages) for their ability to predict rhodopsin structures. Three widely used methodologies were considered: two general methodologies that are commonly applied to soluble proteins and a methodology that uses constraints that are specific for membrane proteins. The test pool consisted of 36 target-template pairs with different sequence similarities that was constructed on the basis of 24 experimental rhodopsin structures taken from the RCSB database. As a result, we showed that all three considered methodologies allow obtaining rhodopsin structures with the quality that is close to the crystallographic one (root mean square deviation (RMSD) of the predicted structure from the corresponding X-ray structure up to 1.5 Å) if the target-template sequence identity is higher than 40%. Moreover, all considered methodologies provided structures of average quality (RMSD < 4.0 Å) if the target-template sequence identity is higher than 20%. Such structures can be subsequently used for further investigation of molecular mechanisms of protein functioning and for the development of modern protein-based biotechnologies.

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Section: Results and Discussionsupporting

confidence: 69%

Section: ■ Methodssupporting

confidence: 69%

A Comparative Study of Modern Homology Modeling Algorithms for Rhodopsin Structure Prediction

et al. 2018

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“…The input files of I-TASSER suite, RosettaCM, Medeller algorithms with corresponding README files, zipped output of I-TASSER suite, scripts for processing structure after homology modeling stage (with instructions in README file), input files for spectra calculations are available: doi, 10.5281/zenodo.229168 32 ( https://zenodo.org/record/229168#.WG5jyFWLTcs)…”

Section: Data Availabilitymentioning

confidence: 99%

A voltage-dependent fluorescent indicator for optogenetic applications, archaerhodopsin-3: Structure and optical properties from in silico modeling

et al. 2017

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It was demonstrated in recent studies that some rhodopsins can be used in optogenetics as fluorescent indicators of membrane voltage. One of the promising candidates for these applications is archaerhodopsin-3. However, the fluorescent signal for wild-type achaerhodopsin-3 is not strong enough for real applications. Rational design of mutants with an improved signal is an important task, which requires both experimental and theoretical studies. Herein, we used a homology-based computational approach to predict the three-dimensional structure of archaerhodopsin-3, and a Quantum Mechanics/Molecular Mechanics (QM/MM) hybrid approach with high-level multireference ab initio methodology (SORCI+Q/AMBER) to model optical properties of this protein. We demonstrated that this methodology allows for reliable prediction of structure and spectral properties of archaerhodopsin-3. The results of this study can be utilized for computational molecular design of efficient fluorescent indicators of membrane voltage for modern optogenetics on the basis of archaerhodopsin-3.

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“…Recently, ARs have attracted much attention, especially, that from Halorubrum sodomense , named AR3, because it can be used in optogenetic studies as a fluorescent indicator of membrane voltage. Precise and quick control of physiological processes using integrated optical and genetic methods has been used in many important applications .…”

Section: Introductionmentioning

confidence: 99%

Two Consecutive Polar Amino Acids at the End of Helix E are Important for Fast Turnover of the Archaerhodopsin Photocycle

Geng

Dai

Chao

et al. 2019

Photochem & Photobiology

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Archaerhodopsins (ARs) is one of the members of microbial rhodopsins. Threonine 164 (T164) and serine 165 (S165) residues of the AR from Halorubrum sp. ejinoor (HeAR) are fully conserved in ARs, although they are far from the proton transfer channel and the retinal Schiff base, and are likely involved in a hydrogen-bonding network at the end of the Helix E where most microbial rhodopsins assume a "bent structure". In the present work, T164 and/or S165 were replaced with an alanine (A), and the photocycles of the mutants were analyzed with flash photolysis. The amino acid replacements caused profound changes to the photocycle of HeAR including prolonged photocycle, accelerated decay of M intermediate and appearance of additional two intermediates which were evident in T164A-and T164A/S165A-HeAR photocyles. These results suggest that although T164 and S165 are located at the far end of the photoactive center, these two amino acid residues are important for maintaining the fast turnover of the HeAR photocycle. The underlying molecular mechanisms are discussed in relation to hydrogenbonding networks involving these two amino acids. Present study may arouse our interests to explore the functional role of the well-conserved "bent structure" in different types of microbial rhodopsin.

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A voltage-dependent fluorescent indicator for optogenetic applications, archaerhodopsin-3: Structure and optical properties from in silico modeling

Cited by 6 publications

References 31 publications

A Comparative Study of Modern Homology Modeling Algorithms for Rhodopsin Structure Prediction

A Comparative Study of Modern Homology Modeling Algorithms for Rhodopsin Structure Prediction

A voltage-dependent fluorescent indicator for optogenetic applications, archaerhodopsin-3: Structure and optical properties from in silico modeling

Two Consecutive Polar Amino Acids at the End of Helix E are Important for Fast Turnover of the Archaerhodopsin Photocycle

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