Seminarium Zakładu Biofizyki

We present an analysis of α-helix folding in the coarse-grained coordinate of number of formed helical hydrogen bonds (NHB) for four alanine peptides (ALA)n, with n = 5, 8, 15 and 21, residues. Based on multi-microsecond all-atom molecular dynamics trajectories in aqueous solution, we represent the system dynamics in a space of hydrogen-bonding microstates. Transitions changing the hydrogen bond count by 1–2 dominate and the coil formation, NHB 1 → 0, is the fastest process. Graf analysis indicates that, at a sufficiently long lag time, folding in the NHB coordinate is consecutive, with direct folding, 0 → 3, for ALA5 and bottlenecks at transitions 4 → 6 for ALA8, 0 → 5 for ALA15 and 0 → 9 for ALA21. Kinetic coarse graining identified crucial folding intermediates and time scales of their formation. Folding is initiated preferentially at both peptide termini. The kinetic model was also used to estimate diffusion and friction coefficients for helix propagation. Use of the low-dimensional hydrogen bonding picture provides a different, complementary way of describing the complex and fascinating mechanism of helix formation as compared to structural analysis.

Bio:Dr. Krzysztof Kuczera received his PhD in Physics from the Institute of Physics of the Polish Academy of Sciences in 1985. He was a postdoctoral fellow at Harvard University over 1986-1991, with Professor Martin Karplus. Since 1992 he has been at the University of Kanas, becoming Professor of Chemistry and Molecular Biosciences in 2007. His research interests are in computer modeling of biomolecular structure, dynamics and interactions. The goals are to relate the simulations to observable experimental properties, and ultimately to explain biological function and design potent and specific drugs. He is the author of more than 130 publications and presenter of more than 180 scientific talks. In the area of teaching he is implementing active learning strategies in chemistry and biochemistry courses has trained 4 postdocs, 15 graduate and 24 undergraduate students. He has been a visiting professor at Baylor University, the University of Texas and Warsaw University.