A biomimetic molecular switch at work: coupling photoisomerization dynamics to peptide structural rearrangement

Abstract

In spite of considerable interest in the design of molecular switches towards photo-controllable (bio)materials, few studies focused on the major influence of the surrounding environment on the switch photoreactivities. We present a combined experimental and computational study of a retinal-like molecular switch linked to a peptide, elucidating the effects on the photoreactivity and on the α-helix secondary structure. Temperature-dependent, femtosecond UV-vis transient absorption spectroscopy and high-level hybrid quantum mechanics/molecular mechanics methods were applied to describe the photoisomerization process and the subsequent peptide rearrangement. It was found that the conformational heterogeneity of the ground state peptide controls the excited state potential energy surface and the thermally activated population decay. Still, a reversible α-helix to α-hairpin conformational change is predicted, paving the way for a fine photocontrol of different secondary structure elements, hence (bio)molecular functions, using retinal-inspired molecular switches.

Reaction dynamics of the chimeric channelrhodopsin C1C2

“…5 , where both optimized all- trans and 13- cis conformations are shown: a water molecule (W2) can compete with Glu162 in the formation of the hydrogen bond with the retinal Schiff base. This alternative active site conformation is indeed related to different excited state energy barriers to reach CI 2 , as recently discussed also in the study of a retinal-like biomimetic photoswitch 37 . In any case, as demonstrated by the single time constant involved in the photoproduct formation through CI 1 , this ground state heterogeneity does not affect the clockwise rotation of the retinal in the excited state (see Fig.…”

Modeling Chemical Reactions by QM/MM Calculations: The Case of the Tautomerization in Fireflies Bioluminescent Systems

“…Many possibilities arise depending on the QM and MM methods used and on the QM/MM interface (Senn and Thiel, 2009 ). Up to now, QM/MM methods have been applied to get insight into different biological issues: (i) enzymatic reaction mechanisms (Friesner and Guallar, 2005 ; Senn and Thiel, 2007 ; Acevedo and Jorgensen, 2010 ), (ii) the calculation of spectroscopic properties (Gascón et al, 2005 ; Sabin et al, 2010 ; Gattuso et al, 2017 ), (iii) the investigation of electronically excited states (Navizet et al, 2010 ; Sabin et al, 2010 ; García-Iriepa et al, 2016 ; Gozem et al, 2017 ) or (iv) the calculation of pKa values (Jensen et al, 2005 ; Riccardi et al, 2006 ). It should be stressed that through QM/MM methods, transition state structures, intermediates and activation energies can be computed, being central for reactivity (Gao et al, 2006 ; Ramos and Fernandes, 2008 ; Lonsdale et al, 2012 ).…”

Steady-State Linear and Non-linear Optical Spectroscopy of Organic Chromophores and Bio-macromolecules

“…Hence, some additional QM/MM studies including polarizable embedding could be worth. Also, it should be mentioned that bio-mimetic photo-switches based on retinal are available, even though still limited to the blue/UV part of spectrum (Sampedro et al, 2004 ; García-Iriepa et al, 2013 , 2016 ), and could hence greatly benefit from computational design to improve TPA properties. In this context it is also important to precise that cross-sections of <10 GM can indeed be detected experimentally, however their increase is fundamental in order to permit the use of TPA switches in practical applications.…”