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S Subbiah

Publications and source records attributed to S Subbiah.

10 recordsLinked to original sources
PubMed1991

Low-resolution real-space envelopes: an approach to the ab initio macromolecular phase problem.

An ab initio approach to the phase problem in macromolecular x-ray crystallography is described. A random gas of hard-sphere point scatterers is allowed to condense under the constraint of the solvent fraction and the restraint of the observed Fourier amplitude data. Two applications to real macromolecular examples are discussed. This method produces an approximate outline of the bulk solvent regions and thus yields a low-resolution picture of the unit cell that can be extended to higher resolutions in special cases, such as through the use of molecular replacement or of noncrystallographic symmetry-based phase extension.

Bacterial Proteins↗
PubMed1991

Prediction of protein side-chain conformation by packing optimization.

We have developed a rapid and completely automatic method for prediction of protein side-chain conformation, applying the simulated annealing algorithm to optimization of side-chain packing (van der Waals) interactions. The method directly attacks the combinatorial problem of simultaneously predicting many residues' conformation, solving in 8 to 12 hours problems for which the systematic search would require over 10(300) central processing unit years. Over a test set of nine proteins ranging in size from 46 to 323 residues, the program's predictions for side-chain atoms had a root-mean-square (r.m.s.) deviation of 1.77 A overall versus the native structures. More importantly, the predictions for core residues were especially accurate, with an r.m.s. value of 1.25 A overall: 80 to 90% of the large hydrophobic side-chains dominating the internal core were correctly predicted, versus 30 to 40% for most current methods. The predictions' main errors were in surface residues poorly constrained by packing and small residues with greater steric freedom and hydrogen bonding interactions, which were not included in the program's potential function. van der Waals interactions appear to be the supreme determinant of the arrangement of side-chains in the core, enforcing a unique allowed packing that in every case so far examined matches the native structure.

Algorithms↗
PubMed1991

Scanning tunneling microscope images of adenine and thymine at atomic resolution.

The scanning tunneling microscope has been used to obtain images of DNA that reveal its major and minor grooves and the direction of helical coiling, but sufficient resolution has not yet been achieved to identify its bases. To determine if this technology is capable of identifying individual DNA bases, we have examined the molecular arrangements of adenine and thymine attached to the basal plane of highly oriented pyrolytic graphite. Both molecules form highly organized lattices following deposition on heated graphite. Lattice dimensions, structural periodicities, and the epitaxy of adenine and thymine molecules with respect to the basal plane of graphite have been determined. Images of these molecules at atomic resolution reveal that the aromatic regions are strongly detected in both molecules while the various side-groups are not well-resolved. These studies provide the first evidence that tunneling microscopy can be used to discriminate between purines and pyramidines.

Adenine↗
PubMed1989

A method for multiple sequence alignment with gaps.

A method that performs multiple sequence alignment by cyclical use of the standard pairwise Needleman-Wunsch algorithm is presented. The required central processor unit time is of the same order of magnitude as the standard Needleman-Wunsch pairwise implementation. Comparison with the one known case where the optimal multiple sequence alignment has been rigorously determined shows that in practice the proposed method finds the mathematically optimal solution. The more interesting question of the biological usefulness of such multiple sequence alignment over pairwise approaches is assessed using protein families whose X-ray structures are known. The two such cases studied, the subdomains of the ricin B-chain and the S-domains of virus coat proteins, have low pairwise similarity and thus fail to align correctly under standard pairwise sequence comparison. In both cases the multiple sequence alignment produced by the proposed technique, apart from minor deviations at loop regions, correctly predicts the true structural alignment. Thus, given many sequences of low pairwise similarity, the proposed multiple sequence method, can extract any familial similarity and so produce a sequence alignment consistent with the underlying structural homology.

Algorithms↗
PubMed1989

A simulated annealing approach to the search problem of protein crystallography.

With the growing availability of computer power it has become routine to perform exhaustive multidimensional searches in protein crystallography. Specifically, in cases where homologous or partially homologous structures are available, the initial interpretation of poor electron density maps is done by performing computer-intensive rotational and translational searches in real space. Often such calculations of the best fit between structure and map cannot even be attempted owing to the vast computing effort involved (years of MicroVax II time). Here, the combinatorial optimization method, simulated annealing, is shown to reduce substantially the computing effort involved and also to permit computations that are beyond the reach of current algorithms. This is illustrated with practical examples involving the structure determinations of the human histocompatibility antigen HLA-A2 and an influenza virus hemagglutinin-sialic acid complex.

Chemical Phenomena↗
PubMed1989

Are coiled-coil proteins evolutionarily related?

A modification to the standard Needleman-Wunsch sequence comparison scheme is presented. In cases where high levels of sequence similarity may arise from a common structural motif, this method discriminates between common ancestry and similarity due to structural constraints alone. Use of this algorithm is illustrated with the coiled-coil motif in the cases of idealized coiled-coil sequences, intermediate filaments and reovirus hemagluttinin.

Algorithms↗
PubMed1989

Structure of the amino-terminal domain of phage 434 repressor at 2.0 A resolution.

The crystal structure of the amino-terminal domain of phage 434 repressor has been solved using molecular replacement methods and refined to an R-factor of 19.3% against data to 2.0 A resolution. The protein comprises five short alpha-helices. Two of these form a helix-turn-helix motif, very similar to those found in related proteins. The protein is remarkably similar to the Cro protein from the same phage.

Amino Acid Sequence↗
PubMed1989

The yeast RAD50 gene encodes a predicted 153-kD protein containing a purine nucleotide-binding domain and two large heptad-repeat regions.

The RAD50 gene of Saccharomyces cerevisiae is required for chromosome synapsis and recombination during meiosis and for repair of DNA damage during vegetative growth. The precise role of the RAD50 gene product in these processes is not known. Most rad50 mutant phenotypes can be explained by the proposal that the RAD50 gene product is involved in the search for homology between interacting DNA molecules or chromosomes, but there is no direct evidence for this model. We present here the nucleotide sequence of the RAD50 locus and an analysis of the predicted 153-kD RAD50 protein. The amino terminal region of the predicted protein contains residues suggestive of a purine nucleotide binding domain, most likely for adenine. The remaining 1170 amino acids consist of two 250 amino acid segments of heptad repeat sequence separated by 320 amino acids, plus a short hydrophobic carboxy-terminal tail. Heptad repeats occur in proteins such as myosin and intermediate filaments that form alpha-helical coiled coils. One of the two heptad regions in RAD50 shows similarity to the S-2 domain of rabbit myosin beyond that expected for two random coiled coil proteins.

Amino Acid Sequence↗
PubMed1988

Recognition of DNA sequences by the repressor of bacteriophage 434.

The structure of a complex between the DNA-binding domain of phage 434 repressor and a 14 base-pair synthetic DNA operator reveals the molecular interactions important for sequence-specific recognition. A set of contacts with DNA backbone, notably involving hydrogen bonds between peptide-NH groups and DNA phosphates, position the repressor and fix the DNA configuration. Direct interactions between amino acid side chains and DNA bases involve nonpolar van der Waals contacts as well as hydrogen bonds. The structures of the repressor domain and of the 434 cro protein are extremely similar. There appear to be no major conformational changes in the proteins when they bind to DNA.

Bacteriophages↗