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School of Biological Sciences

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https://hdl.handle.net/1853/70750

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College of Sciences

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Center for the Study of Systems Biology

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https://finding-aids.library.gatech.edu/agents/corporate_entities/1131

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Publication Search Results

Now showing 1 - 10 of 11

A hierarchical approach to the prediction of the quaternary structure of GCN4 and its mutants

(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.
Computer design of idealized β-motifs

(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.
A reduced model of short range interactions in polypeptide chains

(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.
A simple technique to estimate partition functions and equilibrium constants from Monte Carlo simulations

(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.
A general method for the prediction of the three dimensional structure and folding pathway of globular proteins: Application to designed helical proteins

(Georgia Institute of Technology, 1993-05-01) Kolinski, Andrzej ; Godzik, Adam ; Skolnick, Jeffrey

Starting from amino acid sequence alone, a general approach for simulating folding into the molten globule or rigid, native state depending on sequence is described. In particular, the 3D folds of two simple designed proteins have been predicted using a Monte Carlo folding algorithm. The model employs a very flexible hybrid lattice representation of the protein conformation, and fast lattice dynamics. A full rotamer library for side group conformations, and potentials of mean force of short and long range interactions have been extracted from the statistics of a high resolution set of nonhomologous, 3D structures of globular proteins. The simulated folding process starts from an arbitrary random conformation and relatively rapidly assembles a well defined four helix bundle. The very cooperative folding of the model systems is facilitated by the proper definition of the model protein hydrogen bond network, and multibody interactions of the side groups. The two sequences studied exhibit very different behavior. The first one, in excellent agreement with experiment, folds to a thermodynamically very stable four helix bundle that has all the properties postulated for the molten globule state. The second protein, having a more heterogeneous sequence, at lower temperature undergoes a transition from the molten globule state to the unique native state exhibiting a fixed pattern of side group packing. This marks the first time that the ability to predict a molten globule or a unique native state from sequence alone has been achieved. The implications for the general solution of the protein folding problem are briefly discussed.
A lattice dynamics study of a Langmuir monolayer of monounsaturated fatty acids

(Georgia Institute of Technology, 1993-05-01) Levine, Yehudi K. ; Kolinski, Andrzej ; Skolnick, Jeffrey

A Monte Carlo dynamics (MCD) scheme has been applied in a study of the effects of unsaturated double bonds on the internal conformational dynamics and orientational order of hydrocarbon chains arranged in a monolayer on the surface of an impenetrable interface. The MCD algorithm makes use of the high coordination {2 1 0} lattice for the representation of both sp³ and sp² valence states of the carbon atoms. The chain dynamics are considered to arise from a superposition of local conformational rearrangements. The simulations reproduced the principal features of the experimentally observed order parameter profiles of the C–H bonds on taking into account the intramolecular conformational energy of the molecules and excluded volume effects. The results show that the introduction of a rigid, planar, unsaturated segment enhances the orientational order in the monolayer. The extent of the enhancement is larger for the trans unsaturated chains than for the cis unsaturated ones. The increase in orientational order is accompanied by a marked increase in the effective rotational correlation times, indicating that the unsaturated segments undergo slow and restricted motion. In addition, the C–H bonds of the saturated chain segment between the cis double bond and the headgroup of the chain undergo slower motions than the corresponding vectors in the saturated and trans unsaturated chains. This arises from the anchoring of the headgroup at the impenetrable monolayer interface.
Discretized model of proteins. I. Monte Carlo study of cooperativity in homopolypeptides

(Georgia Institute of Technology, 1992-12-15) Kolinski, Andrzej ; Skolnick, Jeffrey

A discretized model of globular proteins is employed in a Monte Carlo study of the helix-coil transition of polyalanine and the collapse transition of polyvaline. The present lattice realization permits real protein crystal structures to be represented at the level of 1 A resolution. Furthermore, the Monte Carlo dynamic scheme is capable of moving elements of assembled secondary and supersecondary structure. The potentials of mean force for the interactions are constructed from the statistics of a set of high resolution x-ray structures of nonhomologous proteins. The cooperativity of formation of ordered structures is found to be larger when the major contributions to the conformational energy of the low temperature states come from hydrogen bonds and short range conformational propensities. The secondary structure seen in the folded state is the result of an interplay between the short and long range interactions. Compactness itself, driven by long range, nonspecific interactions, seems to be insufficient to generate any appreciable secondary structure. A detailed examination of the dynamics of highly helical model proteins demonstrates that all elements of secondary structure are mobile in the present algorithm, and thus the folding pathways do not depend on the use of a lattice approximation. Possible applications of the present model to the prediction of protein 3D structures are briefly discussed.
Effect of double bonds on the dynamics of hydrocarbon chains

(Georgia Institute of Technology, 1992-07-15) Rey, Antonio ; Kolinski, Andrzej ; Levine, Yehudi K. ; Skolnick, Jeffrey

Brownian dynamics simulations of isolated 18-carbon chains have been performed, both for saturated and unsaturated hydrocarbons. The effect of one or several (nonconjugated) double bonds on the properties of the chains is discussed in terms of both equilibrium and dynamic properties. The introduction of a cis double bond increases the relaxation rates of the unsaturated chain with respect to the saturated alkane. On the other hand, coupling effects in the torsional transitions around a trans double bond make the dynamics of this unsaturated chain very similar to the saturated one. Based on these results, the parameters and moves of a dynamic Monte Carlo algorithm are tuned to reproduce the observed behavior, providing an efficient method for the study of more complicated systems.
Monte Carlo dynamics study of motions in cis-unsaturated hydrocarbon chains

(Georgia Institute of Technology, 1991-09-01) Levine, Yehudi K. ; Skolnick, Jeffrey ; Kolinski, Andrzej

A Monte Carlo dynamics study of the motions of hydrocarbon chains containing cis double bonds is presented. The simulations utilize the high-coordination {2 1 0} lattice for the simultaneous representation of the tetrahedrally bonded carbon atoms and the planar unsaturated segment. Results on single chains undergoing free motion in space and tethered to an impenetrable planar interface are reported. The introduction of a cis double bond into a hydrocarbon chain induces a slowdown in the dynamics. The simulations show this to be a universal result independent of the representation of the chain on the lattice. In contrast, polyunsaturated chains are found to be more mobile than saturated ones.
Static and dynamic properties of a new lattice model of polypeptide chains

(Georgia Institute of Technology, 1991-03-01) Kolinski, Andrzej ; Milik, Mariusz ; Skolnick, Jeffrey

The equilibrium and dynamic properties of a new lattice model of proteins are explored in the athermal limit. In this model, consecutive -carbons of the model polypeptide are connected by vectors of the type (±2,±1,0). In all cases, the chains have a finite backbone thickness which is close to that present in real proteins. Three different polypeptides are examined: polyglycine, polyalanine, and polyleucine. In the latter two cases, the side chains (whose conformations are extracted from known protein crystal structures) are included. For the equilibrium chain dimensions, with increasing side chain bulkiness, the effective chain length is smaller. The calculations suggest that these model polypeptides are in the same universality class as other polymer models. One surprising result is that although polyalanine and polyleucine have chiral sidechains, they do not induce a corresponding handedness of the main chain. For both polyleucine and polyalanine, the scaling of the self-diffusion constant and the terminal relaxation time are consistent with Rouse dynamics of excluded volume chains. Polyglycine exhibits a slightly stronger chain length dependence for these properties. This results from a finite length effect due to moderately long lived, local self-entanglements arising from the thin effective cross section of the chain backbone.