Investigating the Structural Origin of Trpzip2 Temperature Dependent Unfolding Fluorescence lineshape Based on a Markov State Model Simulation

Transcription

1 Investigating the Structural Origin of Trpzip2 Temperature Dependent Unfolding Fluorescence lineshape Based on a Markov State Model Simulation Jian Song 1,2, Fang Gao 3,*, Raymond Z. Cui 4, Feng Shuang 3, Wanzhen Liang 5, Xuhui Huang 4, Wei Zhuang 1, 1 State Key Lab of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Dalian, , China 2 College of Physics and Information Engineering, Henan Normal University, Xinxiang, Henan, , China 3 Institute of Intelligent Machines, Chinese Academy of Sciences, Hefei , China 4 Department of Chemistry, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Hong Kong 5 Department of Chemistry, Xiamen University, Xiamen Figure1: The central 3-MI (3-Methyl indole) unit extracted from trpzip2, and the broken bond is hydrogen saturated.

2 Part1 We present benchmark calculations for 3methyl-indole as shown in Figure 1, which is treated as the first layer in QM/MM hybrid model, to make sure that the employed B3LYP functional is proper for this system. Table 1: The transition energy, main configuration and the corresponding weights, and oscillator strength of 1 L a and 1 L b state of 3-Methylindole in gas phase and water solvent. The optimized geometries are adopted in the excited state calculations, and the water solvent is simulated with the PCM model. The basis set is 6-311g(d,p) for TDDFT, and cc-pvdz for CASPT2. State main configuration Weight (%) excitation energy (ev) oscillator strength B3LYP(vacuum) S 1 ( 1 L a ) H->L S 2 ( 1 L b ) H-1->L H->L B3LYP(water) S 1 ( 1 L a ) H->L S 2 ( 1 L b ) H-1->L H->L LC-BLYP(vacuum) S 1 H-1->L H->L S 2 H->L H-1->L LC-BLYP(water) S 1 H-1->L H->L S 2 H->L H-1->L ωb97x(vacuum) S 1 H-1->L H->L S 2 H->L H-1->L ωb97x(water) S 1 H->L H-1->L S 2 H-1->L H->L CASSCF/CASPT2 1 (vacuum) S 1 ( 1 L b ) H-1->L H->L S 2 ( 1 L a ) H->L

3 Exp.(water) 2 1 L b L a calculated using Molpro package (Ref[2]) 2. from Ref[3] Figure 2: The frontier Kohn-Sham orbitals of 3-Methylindole. HOMO-1 HOMO LUMO LUMO+1 Since the 1 L a excited state of tryptophan is responsible for the emission, a good description of 1 L a state is important in the fluorescence calculation. Several functionals, such as B3LYP and LRC functionals (ωb97x and LC-BLYP), are adopted to calculate the two lowest-lying excited states of 3MI both in vacuum and water. The CASSCF/CASPT2 calculation, which is usually considered as a well description, is also carried out as a benchmarking reference [1]. The excitation energies and the corresponding transition configurations of the first two excited states with different methods are listed in Table 1. As can be seen, the S 1 state of B3LYP in vacuum level is mainly contributed by HOMO to LUMO (66.5%) orbital and the S 2

4 state dominantly comes from HOMO-1 to LUMO (54.3% ) and HOMO to LUMO+1 (43.3% ) transitions. The oscillator strength of S 1 state (about 0.06 ) is larger than that of S 2 state (about 0.02). Correspondingly, the S 1 ( 1 L b ) state of referred CASSCF/CASPT2 is contributed by HOMO-1 to LUMO (46.0%) and HOMO to LUMO+1 (37.1%) and the S 2 ( 1 L a ) state is from HOMO to LUMO (57.0%) orbital. And the oscillator strength of emission 1 L a state is larger than 1 L b state. This means that compared with CASSCF/CASPT2 the two lowest-lying 1 L a and 1 L b state reorder and the S 1 state in B3LYP level is the emission 1 L a state. While with LRC functionals, however, the transition configurations are greatly different from the results of B3LYP and CASPT2: they all mainly from HOMO-1 to LUMO and HOMO to LUMO orbital transitions, but the weight order changes for the two states. Thus it is slightly difficult to assign the two excited states directly. Besides, the oscillator strengths of the two states are closer, which deviates from our known knowledge. Moreover, the excited energies by B3LYP and CASPT2 are closer to experimental results compared with LRC functionals. As seen in Table 3, B3LYP gives the value of 4.66 ev and 4.56 ev for 1 L a in vacuum and water, respectively, and meanwhile CASPT2 gives 4.61 ev in vacuum. All of them are closer to the experimental value of 4.59 ev in water compared with LRC functionals. Part2. Figure3: Fluorescence spectra for two typical folded and unfolded metastates 2 and 7. TCx(0) is the representative conformations of metastate x and RCx(n) is the configuration randomly selected from the top 10 highest probable configurations beside TC.

5 Since this is obviously too expensive to calculate the spectral contributions from all the conformations in all the metastates from MD simulation. We would like to by calculating the fluorescence contributions for a typical folded metastate 2 and a typical unfolded metastate 7. In each state we pick two configurations: The most probable configuration TC and configuration randomly selected from the top 10 highest probable configurations beside TC, which is named RC. We compared spectral lineshape of these four comformations TC2(0), RC2(n), TC7(0) and RC7(n). The spectra are plotted in Figure 3. As seen in figure, The spectra between two macrostates can be distinguished about 10 wavenumber. We conclude that conformations within the same metastable state have relatively similar lineshapes. Part3. Figure 4: The top left panel show the changes of state population η of all the 3MIs at 350K with time. The top right panel α corresponds to η multiplied dipole moment squares. The bottom panel gives the conformations of the first eight largest populated 3MI fluorophores.

6 Figure 5: An example illustration of the A, B, C, D tryptophans in TC-2. Part4. This part demonstrates the six structure parameters used in article. The 1 L a state of tryptophan fluorophores is a typical π π* transition on indole ring. The first two are the bond length alternations (BLAs), which are often used to indicate aromatic character in organic molecules, of pyrrole ring and benzene ring. Another four parameters are dihedral angels. The first two angles represent the twisting character of the two rings, and the second two angles are employed to reflect the noncoplanarity between the two rings. The BLAs of two rings are defined as, BLA BLA DA DA pyrrole benzene = ( B = ( B ) / 3 ( B The first two dihedral angles: pyrrole benzene = ( DA = ( DA DA DA 4 5 ) / 3 ( B ) / The second two dihedral angles: DA = DA DA 1 2 = DA ) / ) / ) / 3

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