Biomedical subjects

Pinak Chakrabarti

Publications and source records attributed to Pinak Chakrabarti.

24 records · Page 2Linked to original sources

PubMed2002

Dissecting protein-protein recognition sites.

The recognition sites in 70 pairwise protein-protein complexes of known three-dimensional structure are dissected in a set of surface patches by clustering atoms at the interface. When the interface buries <2000 A2 of protein surface, the recognition sites usually form a single patch on the surface of each component protein. In contrast, larger interfaces are generally multipatch, with at least one pair of patches that are equivalent in size to a single-patch interface. Each recognition site, or patch within a site, contains a core made of buried interface atoms, surrounded by a rim of atoms that remain accessible to solvent in the complex. A simple geometric model reproduces the number and distribution of atoms within a patch. The rim is similar in composition to the rest of the protein surface, but the core has a distinctive amino acid composition, which may help in identifying potential protein recognition sites on single proteins of known structures.

Amino Acids↗

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↗

PubMed2002

Aromatic-aromatic interactions in and around alpha-helices.

To understand the role of aromatic-aromatic interactions in imparting specificity to the folding process, the geometries of four aromatic residues with different sequence spacing, located in alpha-helices or five residues from helical ends, interacting with each other have been elucidated. The geometry is found to depend on the sequence difference. Specific interactions (C-H...pi and N-H...pi) which result from this geometry may cause a given pair of residues (such as Phe-His) with a particular sequence difference to occur more than expected. The most conspicuous residue in an aromatic pair in the context of helix stability is His, which is found at the last (C1) position or the two positions (Ncap and Ccap) immediately flanking the helix. An alpha-helix and a contiguous 3(10)-helix or two helices separated by a non-helical residue can have interacting aromatic pairs, the geometry of interaction and the relative orientation between the helices being rather fixed. Short helices can also have interacting residues from either side.

Amino Acids, Aromatic↗

PubMed2002

Quantifying the accessible surface area of protein residues in their local environment.

The quantification of the packing of residues in proteins and docking of ligands to macromolecules is important in understanding protein stability and drug design. The number of atoms in contact (within a distance of 4.5 A) can be used to describe the local environment of a residue. As this number increases, the accessible surface area (ASA) of the residue decreases exponentially and the variation can be described in terms of an exponential equation of the form y = a(1)exp(-x/a(2)), each residue having its own set of parameters a(1) and a(2), which also depend on whether the whole residue or just the side chain is considered. Hydrophobic and hydrophilic residues can be distinguished on the basis of both the average number of surrounding atoms and the variation of ASA. For a given number of partner atoms, a comparison of the observed ASA with the expected value obtained from the equation provides a method of assessing the goodness of packing of the residue in a protein structure or its importance in the binding of a ligand. The equation provides a method to estimate the ASA of a protein molecule and the average relative accessibilities of different residues, the latter being inversely correlated with hydrophobicity values.

Amino Acids↗

PubMedDate not supplied

Geometry of interaction of the histidine ring with other planar and basic residues.

Among the aromatic residues in protein structures, histidine (His) is unique, as it can exist in the neutral or positively charged form at the physiological pH. As such, it can interact with other aromatic residues as well as form hydrogen bonds with polar and charged (both negative and positive) residues. We have analyzed the geometry of interaction of His residues with nine other planar side chains containing aromatic (residues Phe, Tyr, Trp, and His), carboxylate (Asp and Glu), carboxamide (Asn and Gln) and guanidinium (Arg) groups in 432 polypeptide chains. With the exception of the aspartic (Asp) and glutamic (Glu) acid side-chains, all other residues prefer to interact in a face-to-face or offset-face-stacked orientation with the His ring. Such a geometry is different from the edge-to-face relative orientation normally associated with the aromatic-aromatic interaction. His-His pair prefers to interact in a face-to-face orientation; however, when both the residues bind the same metal ion, the interplanar angle is close to 90 degrees. The occurrence of different interactions (including the nonconventional N-H...pi and C-H...pi hydrogen bonds) have been correlated with the relative orientations between the interacting residues. Several structural motifs, mostly involved in binding metal ions, have been identified by considering the cases where His residues are in contact with four other planar moieties. About 10% of His residues used here are also found in sequence patterns in PROSITE database. There are examples of the amino end of the Lys side chain interacting with His residues in such a way that it is located on an arc around a ring nitrogen atom.

Amino Acid Motifs↗

PubMedDate not supplied

Interresidue contacts in proteins and protein-protein interfaces and their use in characterizing the homodimeric interface.

The environment of amino acid residues in protein tertiary structures and three types of interfaces formed by protein-protein association--in complexes, homodimers, and crystal lattices of monomeric proteins--has been analyzed in terms of the propensity values of the 20 amino acid residues to be in contact with a given residue. On the basis of the similarity of the environment, twenty residues can be divided into nine classes, which may correspond to a set of reduced amino acid alphabet. There is no appreciable change in the environment in going from the tertiary structure to the interface, those participating in the crystal contacts showing the maximum deviation. Contacts between identical residues are very prominent in homodimers and crystal dimers and arise due to 2-fold related association of residues lining the axis of rotation. These two types of interfaces, representing specific and nonspecific associations, are characterized by the types of residues that partake in "self-contacts"--most notably Leu in the former and Glu in the latter. The relative preference of residues to be involved in "self-contacts" can be used to develop a scoring function to identify homodimeric proteins from crystal structures. Thirty-four percent of such residues are fully conserved among homologous proteins in the homodimer dataset, as opposed to only 20% in crystal dimers. Results point to Leu being the stickiest of all amino acid residues, hence its widespread use in motifs, such as leucine zippers.

Amino Acid Motifs↗