(Georgia Institute of Technology, 1996)
Vieth, Michal; Kolinski, Andrzej; Brooks, C. L., III; Skolnick, Jeffrey
A hierarchical approach to protein folding is employed to examine the folding pathway and predict the quaternary structure of the GCN4 leucine zipper. Structures comparable in quality to experiment have been predicted. In addition, the equilibrium between dimers, trimers and tetramers of a number of GCN4 mutants has been examined. In five out of eight cases, the simulation results are in accordance with the experimental studies of Harbury, et al.
(Georgia Institute of Technology, 1995-12-15)
Kolinski, Andrzej; Galazka, Wojciech; Skolnick, Jeffrey
A lattice model of protein conformation and dynamics is used to explore the requirements for the de novo folding from an arbitrary random coil state of idealized models of four and six-member β-barrels. A number of possible conjectures for the factors giving rise to the structural uniqueness of globular proteins are examined. These include the relative role of generic hydrophilic/ hydrophobic amino acid patterns, the relative importance of the specific identity of the hydrophobic amino acids that form the core of the protein and the possible role played by polar groups in destabilizing alternative, misfolded conformations. These studies may also provide some insights into the relative importance of short range interactions, cooperative hydrogen bonding and tertiary interactions in determining the uniqueness of the native state, as well as the cooperativity of the folding process. Thus, these simulations may provide guidelines for the early stages of the protein design process. Possible applications to the general protein folding problem are also briefly discussed.
(Georgia Institute of Technology, 1995-09-08)
Kolinski, Andrzej; Milik, Mariusz; Rycombel, Jakub; Skolnick, Jeffrey
A simple model of short range interactions is proposed for a reduced lattice representation of polypeptide conformation. The potential is derived on the basis of statistical regularities seen in the known crystal structures of globular proteins. This potential accounts for the generic stiffness of polypeptides, the correlation between peptide bond plates, and the sequence dependent correlations between consecutive segments of the C-trace. This model is used for simulation of the equilibrium and dynamic properties of polypeptides in the denatured state. It is shown that the proposed factorization of the local conformational propensities reproduces secondary structure tendencies encoded in the protein sequence. Possible applications for modeling of protein folding are briefly discussed.
(Georgia Institute of Technology, 1995-04-15)
Vieth, Michal; Kolinski, Andrzej; Skolnick, Jeffrey
A combined Monte Carlo (MC) simulation-statistical mechanical treatment is proposed to calculate the internal partition function and equilibrium constant. The method has been applied to a number of one and multidimensional analytical functions. When sampling is incomplete, various factorization approximations for estimating the partition function are discussed. The resulting errors are smaller when the ratios of the partition functions are calculated (as in the determination of equilibrium constants) as opposed to the partition function itself.