Search PubMed⌕ Search

Biomedical subjects

A Godzik

Publications and source records attributed to A Godzik.

63 records · Page 4Linked to original sources
PubMed1992

Simulations of the folding pathway of triose phosphate isomerase-type alpha/beta barrel proteins.

Simulations of the folding pathways of two large alpha/beta proteins, the alpha subunit of tryptophan synthase and triose phosphate isomerase, are reported using the knight's walk lattice model of globular proteins and Monte Carlo dynamics. Starting from randomly generated unfolded states and with no assumptions regarding the nature of the folding intermediates, for the tryptophan synthase subunit these simulations predict, in agreement with experiment, the existence and location of a stable equilibrium intermediate comprised of six beta strands on the amino terminus of the molecule. For the case of triose phosphate isomerase, the simulations predict that both amino- and carboxyl-terminal intermediates should be observed. In a significant modification of previous lattice models, this model includes a full heavy atom side chain description and is capable of representing native conformations at the level of 2.5- to 3-A rms deviation for the C alpha positions, as compared to the crystal structure. With a well-balanced compromise between accuracy of the protein description and the computer requirements necessary to perform simulations spanning biologically significant amounts of time, the lattice model described here brings the possibility of studying important biological processes to present-day computers.

Animals↗
PubMed1989

Conservation of residue interactions in a family of Ca-binding proteins.

In the TNC family of Ca-binding proteins (calmodulin, parvalbumin, intestinal calcium binding protein and troponin C) approximately 70 well-conserved amino acid sequences and six crystal structures are known. We find a clear correlation between residue contacts in the structures and residue conservation in the sequences: residues with strong sidechain-sidechain contacts in the three-dimenesional structure tend to be the more conserved in the sequence. This is one way to quantify the intuitive notion of the importance of sidechain interactions for maintaining protein three-dimensional structure in evolution and may usefully be taken into account in planning point mutations in protein engineering.

Amino Acid Sequence↗
PubMed1988

On the interactions of charged side chains with the alpha-helix backbone.

The effects of the position of charged amino acid side chains on the stability of the alpha-helix are investigated. Calculations for the model polyAla 13 residue alpha-helix, with modifications based on experimental work, are performed at three levels of approximation. The observed stabilization of the alpha-helix could be explained by interactions between its macrodipole and charged amino acid side chains. Limitations of the model are discussed.

Amino Acids↗
PubMed1988

Conformational role of His-12 in C-peptide of ribonuclease A.

Possible interactions of the His-12 ring with other side chain and backbone groups of C-peptide lactone (CPL) are discussed. The works published so far are critically reviewed and compared with the latest results obtained by the authors. The main new conclusion is that in the helical conformation of CPL, the Phe-8 and His-12 rings are clustered together. Studies of Phe-8----Ala analogs of CPL and calculations of ring current effects satisfactorily explain the observed environmental shifts of Phe-8 and His-12 protons in NMR spectra of CPL. Interaction between both rings is favorable for alpha-helix formation, but cannot explain an increase in helix stability related with protonation of His-12. This effect arises from favorable interactions of the charged His+-12 ring with the helix backbone.

Histidine↗
PubMed1987

The Monte Carlo simulation of pearl chain formation.

The phenomenon of pearl chain formation (PCF) is investigated by means of a statistical model using the Monte Carlo method. Fifteen particles (cells) interacting with simple dipole-dipole potential are shown to form chains under the influence of an external field with a threshold potential significantly lower than the two particle estimate. A possible overlap between PCF and the thermal effects of an electric field is suggested.

Algorithms↗
PubMed1987

Calculations of the conformational properties of acyclonucleosides. Part I. Stable conformations of acyclovir.

Conformational properties of te antiherpes agent acyclovir (acycloguanosine, ACG) were calculated using molecular mechanics approximation. Eighty two different stable conformations have been determined. The large number of local minima of the total enery, and small differences between them, point to the marked flexibility of the acyclic chain. The barrier to rotation around N9-C1 bond was calculated and found to be asymmetric (the lower equals 17 kJ/mol, the higher 63 kJ/mol). An energetic preference for the compact from of ACG was demonstrated. A comparison of the calculated conformations with the crystallographic structures is presented.

Acyclovir↗
PubMedDate not supplied

Fold predictions for bacterial genomes.

Fold assignments for newly sequenced genomes belong to the most important and interesting applications of the booming field of protein structure prediction. We present a brief survey and a discussion of such assignments completed to date, using as an example several fold assignment projects for proteins from the Escherichia coli genome. This review focuses on steps that are necessary to go beyond the simple assignment projects and into the development of tools extending our understanding of functions of proteins in newly sequenced genomes. This paper also discusses several problems seldom addressed in the literature, such as the problem of domain prediction and complementary predictions (e.g., transmembrane regions and flexible regions) and cross-correlation of predictions from different servers. The influence of sequence and structure database growth on prediction success is also addressed. Finally, we discuss the perspectives of the field in the context of massive sequence and structure determination projects, as well as the development of novel prediction methods.

Algorithms↗