The thermodynamics of charge transfer in DNA photolyase: using thermodynamic integration calculations to analyse the kinetics of electron transfer reactions

• Published in: Physical chemistry chemical physics : PCCP Vol. 12; no. 32; pp. 9516 - 9525
• Main Authors: Krapf, Sebastian, Koslowski, Thorsten, Steinbrecher, Thomas
• Format: Journal Article
• Language: English
• Published: Cambridge Royal Society of Chemistry 01.01.2010
• Subjects: Chemistry; Deoxyribodipyrimidine Photo-Lyase - chemistry; Electron Transport; Exact sciences and technology; General and physical chemistry; Kinetics; Molecular Dynamics Simulation; Quantum Theory; Thermodynamics; Theory; Molecular dynamics; Electron transfer; Tryptophan; Flexibility; Free energy; Mechanism; Protein; Thermodynamics; Quantum computation; Transfer reaction; Residue; Aminoacid; DNA; Calculation; Kinetics; Thermodynamic properties; Charge transfer; Transport
• ISSN: 1463-9076; 1463-9084; 1463-9084
• DOI: 10.1039/c000876a

DNA Photolyases are light sensitive oxidoreductases present in many organisms that participate in the repair of photodamaged DNA. They are capable of electron transfer between a bound cofactor and a chain of tryptophan amino acid residues. Due to their unique mechanism and important function, photolyases have been subject to intense study in recent times, with both experimental and computational efforts. In this work, we present a novel application of classical molecular dynamics based free energy calculations, combined with quantum mechanical computations, to biomolecular charge transfer. Our approach allows for the determination of all reaction parameters in Marcus' theory of charge transport. We were able to calculate the free energy profile for the movement of a positive charge along protein sidechains involved in the biomolecule's function as well as charge-transfer rates that are in good agreement with experimental results. Our approach to simulate charge-transfer reactions explicitly includes the influence of protein flexibility and solvent dynamics on charge-transfer energetics. As applied here to a biomolecular system of considerable scientific interest, we believe the method to be easily adaptable to the study of charge-transfer phenomena in biochemistry and other fields. Combined molecular dynamics, free energy and quantum mechanical calculations allow the determination of all the Marcus parameters of charge transfer in CPD photolyases.