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Debnath Pal

Publications and source records attributed to Debnath Pal.

6 recordsLinked to original sources
PubMed2005

Inference of protein function from protein structure.

Structural genomics has brought us three-dimensional structures of proteins with unknown functions. To shed light on such structures, we have developed ProKnow (http://www.doe-mbi.ucla.edu/Services/ProKnow/), which annotates proteins with Gene Ontology functional terms. The method extracts features from the protein such as 3D fold, sequence, motif, and functional linkages and relates them to function via the ProKnow knowledgebase of features, which links features to annotated functions via annotation profiles. Bayes' theorem is used to compute weights of the functions assigned, using likelihoods based on the extracted features. The description level of the assigned function is quantified by the ontology depth (from 1 = general to 9 = specific). Jackknife tests show approximately 89% correct assignments at ontology depth 1 and 40% at depth 9, with 93% coverage of 1507 distinct folded proteins. Overall, about 70% of the assignments were inferred correctly. This level of performance suggests that ProKnow is a useful resource in functional assessments of novel proteins.

Amino Acid Motifs↗
PubMed2004

Disulfide bonds, their stereospecific environment and conservation in protein structures.

We studied the specificity of the non-bonded interaction in the environment of 572 disulfide bonds in 247 polypeptide chains selected from the Protein Data Bank. The preferred geometry of interaction of peptide oxygen atoms is along the back of the two covalent bonds at the sulfur atom of half cystine. With aromatic residues the geometries that direct one of the sulfur lone pair of electrons into the aromatic pi-system are avoided; an orientation in which the sulfide plane is normal or inclined to the aromatic plane and on top of its edge is normally preferred. The importance of the S...aromatic interaction is manifested in the high degree of its conservation across members in homologous protein families. These interactions, while providing extra overall stability to the native fold and reducing the accessibility of the disulfide bond and thereby preventing exchange reactions, also set the orientation of the conserved aromatic rings for further interactions and binding to another molecule. The conformational features and the mode of interactions of disulfide bridges should be useful for molecular design and protein engineering experiments.

Amino Acids, Aromatic↗
PubMed2002

Secondary structures at polypeptide-chain termini and their features.

An analysis of secondary structures (alpha-helices and beta-strands) in the two terminal regions of polypeptide chains reveals features different from those observed over the whole protein structure. Compared with the overall distribution, the helices in the N-terminal region tend to be smaller and have higher propensities to contain Gln and Leu, while the C-terminal helices are longer and have a greater proportion of Lys and Glu. As a strand, the C-terminal region is never found in the interior of parallel beta-sheets and has a higher propensity to be at the edge of antiparallel beta-sheets. In contrast, compared with the whole structure the N-terminal region has a higher propensity to be in the interior of parallel beta-sheets. Compared with the overall distributions, terminal helices and strands show distinct periodicities in length. The Schellman motif, which is a prevalent C-capping motif in helices, is not common in C-terminal helices. There are other observations that can be used in the design of helical peptides: more residues beyond the C-terminus of helices are used for capping interactions than residues before the N-terminus. Consideration of the distribution of terminal strands in the interior and at the edge of beta-sheets suggests a sequential folding mechanism beginning at the N-terminus of the polypeptide chain.

Amino Acid Sequence↗
PubMed2002

An overview on 2-methyl-2,4-pentanediol in crystallization and in crystals of biological macromolecules.

2-Methyl-2,4-pentanediol (MPD) is the most popular chemical additive used for crystallization of biological macromolecules. However, the mechanism of its action on proteins in aqueous solution is not well understood. We have carried out a systematic analysis of the conformation and environment of MPD molecules bound to proteins. We find that the majority of MPD molecules adopt their most stable conformer. They prefer to bind to hydrophobic sites with a distinct preference for leucine side chains. Most MPD binding sites involve amino-acid residues in helical or beta-sheet structures. MPD binding to proteins is penetrative, leading to displacement of water molecules in grooves and cavities (sometimes ligand-binding and active sites) on the protein surface. This results in a large reduction of solvent-accessible area, which can have significant implications for protein stability. The packing of the MPD molecules by the protein is not optimal and usually some other solvent molecules are also bound along with it. Our analysis suggests that MPD is not as strong a denaturant as often suggested. It promotes stabilization of the protein by preferential hydration, which is facilitated by attachment of MPD molecules to the hydrophobic surface.

Binding Sites↗
PubMed2002

On residues in the disallowed region of the Ramachandran map.

An analysis of the occurrence of nonglycyl residues in conformations disallowed in the Ramachandran plot is presented. Ser, Asn, Thr, and Cys have the highest propensities to exhibit such conformations, and the branched aliphatic residues the lowest. Residues cluster in five regions and there are some trends in the types of residues and their side-chain conformations (chi(1)) occupying these. Majority of the residues are found at the edge of helices and strands and in short loops, and are involved in different types of weak, stabilizing interactions. A structural motif has been identified where a residue in disallowed conformation occurs as the first residue of a short 3(10)-helix. On the basis of the types of neighboring residues, the location in the three-dimensional structure and accessibility, there are similarities with the occurrence of cis peptide bonds in protein structures.

Algorithms↗