Simulation of Proton Transfer in Biological Systems Hong Zhang, Sean Smith Centre for Computational Molecular Science, University of Queensland, Brisbane QLD 4072 Australia 1 Introduction Proton transfer plays a vital role in biological systems — Green Fluorescent Protein (GFP): monitoring of protein-folding, gene expression, protein movement and cell development. EVB state 1 2 Methodology QD: transferring protons. 3 Preliminary Results  The characteristic first passage time for proton/deuteron transfer are computed and corresponding isotope effect is compared with the measured one (in qualitatively agreement).  The calculated vibrational period for oscillation of the proton on the excited state is 73.5 fs at the excitation wavelength of 400 nm, which is in agreement with the experimental result from EGFP.  The origin of the early-time (prompt) stimulated emission is tentatively explained in terms of off-resonance excitation at 400 nm and contribution from the fastest component for proton transfer in GFP. Currently we are exploring to use more sophisticated methods including mixed quantum dynamics/molecular dynamics method for GFP simulation.  GROMOS: extend our QD codes into the context of Gromos package.  Introduce new coupling scheme between QD and MD part.  CPMD/GROMOS + QD: A QM/MM QD/MD package. Fig. 2. Evolving excited state wavepackets for proton motions at four distinctive stages for off–resonance excitation case at 400 nm. (a) -30 fs to -25 fs. Photo-absorption processes are shown. (b) 10 fs to 15 fs. Some wave packets excited to the upper surface dump back onto the ground state. (c) 34 fs to 37 fs. Fastest component of proton transfer has appeared. (d) 72 fs to 74 fs. Most of the packets has moved back into A* well. Recent results from model real time quantum calculations of proton transfer in GFP regarding 4 electronic states (labeled A, A*, I, I*) are presented. Important processes (photo-absorption and proton-transfer in the excited state); The vibrational period on the excited state; The isotope effect of proton transfer; The origin of the early-time stimulated emission is tentatively explained Recent results from model real time quantum calculations of proton transfer in GFP regarding 4 electronic states (labeled A, A*, I, I*) are presented.  Important processes (photo-absorption and proton-transfer in the excited state);  The vibrational period on the excited state;  The isotope effect of proton transfer;  The origin of the early-time stimulated emission is tentatively explained. EVB state 2 The proposed mechanism for the photoisomerization of wild-type GFP is from the neutral form of the chromophore (A) which converts to the anionic form (B) by going through the intermediate state (I). By using mixed quantum/classical calculations, hopefully we can predict the whole process of the proton transfer. Challenges: both electronic and nuclear quantum effects, motion of protein environment. Hong Zhang, Dr. Research Fellow and Q&M Dynamics Group Leader Centre for Computational Molecular Science Chemistry Building 68, The University of Queensland Qld 4072, Brisbane. tel: (617) web: / / DA H DA H Zhang & Smith, Phys Chem Chem Phys, 6, , 2004 (invited review). Zhang & Smith, Phys Chem Comm, 6, 12-20, 2003 (invited review). Zhang & Smith, Chem Phys, 308, , Zhang & Smith, J Chem Phys, 2005 (accepted). Zhang & Smith, J Chem Phys 120: , Zhang & Smith, J Chem Phys 120: , Zhang & Smith, Phys Chem Chem Phys 6: Zhang & Smith, J Chem Phys 118: , Zhang & Smith, J Theor Comput Chem, 2, , Zhang & Smith, J Chem Phys 117: , Zhang & Smith, J Phys Chem A 106: , Zhang & Smith, J Phys Chem A 106: , Zhang & Smith, J Chem Phys 116: , Zhang & Smith, Chem Phys Lett 347: , Zhang & Smith, J Chem Phys 115: , Zhang & Smith, Phys Chem Chem Phys 3: , Fig. 1. Model potential energy surfaces of ground state (a) and excited state (b) in GFP. Open circles are from the suggested illustrative PESs given by Vöhringer et al., while solid lines are the interpolated full PESs used in the simulation. Fig. 3. (a) Time evolution of excited-state population for off-resonance excitation at 400 nm. Solid line represents proton transfer case while dashed line represents deuteron transfer case. (b) Same as in (a), but for on-resonance excitation case at 434 nm. 4 Conclusions and Future Work 5 Some Related Publications   Lanczos representation method;   Real Chebyshev method;   FFT/split operator method. 2)QM/MM method.   DFT in CPMD: chromophore;   GROMOS force field: all other atoms. MD: all other atoms.   GROMOS;   Car-Parrinello Molecular Dynamics. PES: 1)empirical valence bond.