Matching simulation and experiment (extended abstract)

Jon M. Sorenson, Teresa Head-Gordon
2000 Proceedings of the fourth annual international conference on Computational molecular biology - RECOMB '00  
Simulations of simplified protein folding models have provided much insight into solving the protein folding problem. We propose here a new off-lattice bead model, capable of simulating several different fold classes of small proteins. We present the sequence for an a/~ protein resembling the IgG-binding proteins L and G. The thermodynamics of the folding process for this model are characterized using the multiple multi-histogram method combined with constant-temperature Langevin simulations.
more » ... evin simulations. The folding is shown to be highly cooperative, with chain collapse nearly accompanying folding. Two parallel folding pathways are shown to exist on the folding free energy landscape. One pathway contains an intermediate--similar to experiments on protein G, and one pathway contains no intermediates--similar to experiments on protein L. The folding kinetics are characterized by tabulating mean-first passage times, and we show that the onset of glasslike kinetics occurs at much lower temperatures than the folding temperature. This model is expected to be useful in many future contexts: investigating questions of the role of local versus non-local interactions in various fold classes, addressing the effect of sequence Permission to make dtgltal or hard copras of all or part oftlus work for pe~sonat or classroom use ~s granted without lee prm, lded that copies are not made or dmtnbutcd for profit ol eommc~cml advantage and that copras bear th~s notme and the full c~tatlon on the first page 1o copy otherwise, to repubhsh, to post on servers or to redistribute to hsts. requires prior specll]C permission and/or a tee RECOMB 2000 Tokyo Japan USA Copyright ACM 2000 1-58113-186-0/00/04 $5.00 mutations affecting secondary structure propensities, and providing a computationally feasible model for studying the role of solvation forces in protein folding.
doi:10.1145/332306.332565 dblp:conf/recomb/SorensonH00 fatcat:3pfldlo7xngrpkolz7izr7yt5m