title: Photodynamics of Lys+-Trp protein motifs: hydrogen bonds ensure photostability.
abstract: Cation-pi interactions such as Lys(+)-Trp, are highly abundant structural motifs in proteins. Both, experimental and theoretical studies of small prototypical gas phase systems, H+Trp, H+Trp x (H2O)n and H+Gly-Trp, indicate such an arrangement as potential hot spot for photodamage and photoinstability. Here, we study the photodynamical properties of a Lys(+)-Trp pair in the protein human serum albumin (HSA) using nonadiabatic mixed time-dependent density functional theory/molecular mechanics simulations (TDDFT/MM). These simulations show that the findings for small protonated Trp complexes are largely transferable to a more complex protein environment. Under partially hydrated ("dry" conditions), when the -NH3+ head group is not fully solvated, photoexcitation of the tryptophan leads indeed to rapid photodissociation of the proximal charged amino group. In contrast, photostability is well maintained under fully solvated conditions when the lysine head group is fully hydrogen-bonded. In this case, photodynamics takes place in a pi-pi* state without interference of fast dissociative sigma*C-N) or sigma*N-H channels. These results highlight the crucial role of hydrogen bonds in ensuring the photostability of essential biological building blocks.
authors.affiliation: Laboratory of Computational Chemistry and Biochemistry, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
authors.forename: Matteo
authors.initials: M
authors.lastname: Guglielmi
authors.forename: Manuel
authors.initials: M
authors.lastname: Doemer
authors.forename: Ivano
authors.initials: I
authors.lastname: Tavernelli
authors.forename: Ursula
authors.initials: U
authors.lastname: Rothlisberger
mesh_terms: D020816:Amino Acid Motifs; D006801:Humans; D006860:Hydrogen Bonding; D055668:Photochemical Processes; D011487:Protein Conformation; D055550:Protein Stability; D012709:Serum Albumin / Q000737:chemistry; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D012709:Serum Albumin; D014364:Tryptophan