Search for fluorescent Rhodopsins with multiconfigurational quantum chemistry based QM/MM models

• Grant number: 13/11634-0
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• Start date: October 01, 2013
• End date: September 30, 2014
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Physical-Chemistry
• Principal Investigator: Sylvio Roberto Accioly Canuto
• Grantee: Yoelvis Orozco González
• Supervisor: Massimo Olivucci
• Host Institution: Instituto de Física (IF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: Bowling Green State University (BGSU), United States
• Associated to the scholarship: 12/15161-7 - Solvent effect on excited electronic states dynamics and on nonradioactive deactivation mechanisms, BP.PD

Abstract

Fluorescent proteins have been used in the past decade in numerous applications as genetically encoded sensing probes in living cells, acting as fluorescent indicators to track and quantify specic biochemical and biophysical parameters in the complex environment of the cell. These techniques are proving to be extremely useful, providing new insights into the molecular mechanisms of cellular processes. Although the green fluorescent protein (GFP) and its variants are presently the most used as encoding sensing probes, recent theoretical works have indicated that it may be possible to use derivatives of the rhodopsin family as fluorescent proteins. In fact, some preliminary and promising results have shown the Anabaena Sensory Rhodopsin (ASR) as a photochromic system, able to interconvert between different excited electronic states by changing the irradiation wavelength, making it a good candidate for the design of light-responsive genetically encoded cellular switches. Then, in this project we will work to design in silico new mutants of the ASR, capable of isomerizing more quickly than wild type ASR with the aim of improving its properties as genetically encoded cellular switches. And, working in the opposite direction we will try to introduce mutations in the protein that slow down or even stop the isomerization of the chromophore, which can help in the design of novel genetically encoded fluorescent sensing probes. To achieve these objectives we will study the variations of the excited electronic states potential energy surfaces of the chromophore as result of chemical mutations in the surrounded protein. The hybrid Quantum Mechanical/Molecular Mechanical (QM/MM) model of ASR, has proved to be very favorable for this task. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

OROZCO-GONZALEZ, YOELVIS; MANATHUNGA, MADUSHANKA; MARIN, MARIA DEL CARMEN; AGATHANGELOU, DAMIANOS; JUNG, KWANG-HWAN; MELACCIO, FEDERICO; FERRE, NICOLAS; HAACKE, STEFAN; COUTINHO, KALINE; CANUTO, SYLVIO; et al. An Average Solvent Electrostatic Configuration Protocol for QM/MM Free Energy Optimization: Implementation and Application to Rhodopsin Systems. JOURNAL OF CHEMICAL THEORY AND COMPUTATION, v. 13, n. 12, p. 6391-6404, DEC 2017. (13/11634-0, 12/15161-7)