(Georgia Institute of Technology, 1995-10)
Milik, Mariusz; Skolnick, Jeffrey
A Monte Carlo Dynamics simulation was used to investigate the behavior of filamentous bacteriophage coat proteins in a model membrane environment. Our simulation agrees with the previous experimental observations that despite the low sequence similarity between the major coat proteins of Pf1 and fd bacteriophages, their structure in the membrane environment is very similar. These results support the hypothesis that the hydrophobic effect exerts an important influence on membrane protein structure. The model may also be used for modeling the insertion and transport processes in protein-membrane systems. The example of fd protein was also used as a test of sensitivity of our model to temperature, thickness of the hydrocarbon phase, and simulation time. In all cases, the results were independent (over the tested range) of the particular values of the parameters.
(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)
Milik, Mariusz; Skolnick, Jeffrey
A system is presented for generating peptide sequences with desirable properties,
using combination of neural network and artificial evolution. The
process is illustrated by an example of a practical problem of generating
artificial transbilayer peptides. The peptides generated in the process of
artificial evolution have the physico-chemical properties of transmembrane
peptides, and forms stable transmembrane structures in testing Monte Carlo
simulations. The artificial evolution system is designed to emulate natural
evolution; therefore it is of both practical and theoretical interest, both in
terms of rational design of protein sequences and modeling of natural evolution
of proteins.