Small single-domain proteins often exhibit only a single free-energybarrier, or transition state, between the denatured and the native state.The folding kinetics of these proteins is usually explored via mutationalanalysis. A central question is which structural information on thetransition state can be derived from the mutational data. To inter...
Creator:
Weikl, Thomas (Max Planck Institute for Colloids and Interfaces)
Created:
2008-01-17
Contributed By:
University of Minnesota, Institute for Mathematics and its Applications.
Globally the energy landscape of a folding protein resembles a partially rough funnel. The local roughness of the funnel reflects transient trapping of the protein configurations in local free energy minima. The overall funnel shape of the landscape, superimposed on this roughness, arises because the interactions present in the native structure ...
Creator:
Onuchic, José Nelson (University of California, San Diego)
Created:
2008-01-17
Contributed By:
University of Minnesota, Institute for Mathematics and its Applications.
Lead generation is a major hurdle in small-molecule drug discovery, with an estimated 60% of projects failing from lack of lead matter or difficulty in optimizing leads for drug-like properties. It would be valuable to identify these less-druggable targets before incurring substantial expenditure and effort. We discovered that a model-based appr...
Creator:
Cheng, Alan C. (Amgen Cambridge Research Center)
Created:
2008-01-17
Contributed By:
University of Minnesota, Institute for Mathematics and its Applications.
We focus on the problem of determining the structure of complexes formed by the association of two proteins by searching for the global minimum of a function approximating the free energy of the complex. Solving this problem requires the combination of a number of different optimization methods. First we explore the conformational space by syste...
Creator:
Vajda, Sandor (Boston University)
Created:
2008-01-17
Contributed By:
University of Minnesota, Institute for Mathematics and its Applications.
Coarse master equations and diffusion models provide powerful tools to study the equilibrium and non-equilibrium properties of molecular systems. Maximum likelihood and Bayesian approaches have been used successfully to construct such models from the observed dynamics projected onto discrete and continuous low-dimensional sub-spaces. By using a ...
Creator:
Hummer, Gerhard (National Institutes of Health (NIH))
Created:
2008-01-17
Contributed By:
University of Minnesota, Institute for Mathematics and its Applications.
Many small single-domain proteins undergo cooperative, switch-likefolding/unfolding transitions with very low populations of intermediate,i.e., partially folded, conformations. The phenomenon of cooperative foldingis not readily accounted for by common notions about driving forces for folding. I will discuss how common protein chain models with ...
Creator:
Chan, Hue-Sun (University of Toronto)
Created:
2008-01-17
Contributed By:
University of Minnesota, Institute for Mathematics and its Applications.
Recent progress in obtaining docked protein complexes will be discussed.The combination of exhaustive search, clustering and localized globaloptimization can reliably find energy minima to highly nonconvex biomolecularenergy functions. Using an energy function that adds desolvation andscreened electrostatics to classical molecular mechanics pote...
Creator:
Mitchell, Julie C. (University of Wisconsin, Madison)
Created:
2008-01-17
Contributed By:
University of Minnesota, Institute for Mathematics and its Applications.