TY - JOUR

T1 - A voltage-dependent fluorescent indicator for optogenetic applications, archaerhodopsin-3

T2 - Structure and optical properties from in silico modeling

AU - Ryazantsev, Mikhail N.

AU - Николаев, Дмитрий Михайлович

AU - Emelyanov, Anton

AU - Boitsov, Vitaly M.

AU - Panov, Maxim S.

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Archaerhodopsin

KW - Optogenetics

KW - Protein structure prediction

KW - QM/MM

KW - Spectral tuning in rhodopsins

UR - http://www.scopus.com/inward/record.url?scp=85017347827&partnerID=8YFLogxK

U2 - 10.12688/f1000research.10541.2

DO - 10.12688/f1000research.10541.2

M3 - Article

VL - 6

JO - F1000Research

JF - F1000Research

SN - 2046-1402

M1 - 33

ER -