Protein sequencing molecular biology

The ability to sequence proteins at low levels and sometimes in a high throughput fashion has considerably advanced protein-oriented molecular biological research. The qualitative change affects the two criteria sensitivity and throughput. 

Murzin A G, S E Brenner, T Hubbard and C Chothia 1995. SCOP A Structural Classification of Proteins Database for the Investigation of Sequences and Structures. Journal of Molecular Biology 247 536-540. 

Needleman S B and C D Wunsch 1970. A General Method Applicable to the Search for Similarities in the Amino Acid Sequences of Two Proteins. Journal of Molecular Biology 48 443-453. 

Ortiz A R, A Kolinski and J Skolnick 1998. Fold Assembly of Small Proteins Using Monte C Simulations Driven by Restraints Derived from Multiple Sequence Alignments. Jourru Molecular Biology 277 419-446. 

TL Bailey, M Grihskov. The megaprior heuristic for discovering protein sequence patterns. Intelligent Systems in Molecular Biology 4 15-24, 1996. 

To understand the biological function of proteins we would therefore like to be able to deduce or predict the three-dimensional structure from the amino acid sequence. This we cannot do. In spite of considerable efforts over the past 25 years, this folding problem is still unsolved and remains one of the most basic intellectual challenges in molecular biology. 

Arthur Lesk and Cyrus Chothia at the MRC Laboratory of Molecular Biology in Cambridge, UK, compared the family of globin strucfures with the aim of answering two general questions How can amino acid sequences that are very different form proteins that are very similar in their three-dimensional structure What is the mechanism by which proteins adapt to mutations in the course of their evolution ... 

The World Wide Web has transformed the way in which we obtain and analyze published information on proteins. What only a few years ago would take days or weeks and require the use of expensive computer workstations can now be achieved in a few minutes or hours using personal computers, both PCs and Macintosh, connected to the internet. The Web contains hundreds of sites of Interest to molecular biologists, many of which are listed in Pedro s BioMolecular Research Tools (http // www.fmi.ch/biology/research tools.html). Many sites provide free access to databases that make it very easy to obtain information on structurally related proteins, the amino acid sequences of homologous proteins, relevant literature references, medical information and metabolic pathways. This development has opened up new opportunities for even non-specialists to view and manipulate a structure of interest or to carry out amino-acid sequence comparisons, and one can now rapidly obtain an overview of a particular area of molecular biology. We shall here describe some Web sites that are of interest from a structural point of view. Updated links to these sites can be found in the Introduction to Protein Structure Web site (http // WWW.ProteinStructure.com/). 

Moreover, molecular modeling is one key method of a wide range of computer-assisted methods to analyze and predict relationships between protein sequence, 3D-molecular structure, and biological function (sequence-structure-function relationships). In molecular pharmacology these methods focus predominantly on analysis of interactions between different proteins, and between ligands (hormones, drugs) and proteins as well gaining information at the amino acid and even to atomic level. 

Several attempts were made to apply nanostructures made of DNA or proteins to the development of alternative computation or computer memory. The concept of DNA computing was developed as an alternative computation approach based on information and data stored as sequenced DNA nucleotides and DNA-specific hybridization and elongation as a means to reach the answer or solution to a problem. Available tools of molecular biology were employed to identify and analyze the results [66-68]. This multistage computation is based on the assumption that solutions can be sought in parallel, thus compensating for the relatively slow processing time. 

Selective cleavage of peptides and proteins is an important procedure in biochemistry and molecular biology. The half-life for the uncatalyzed hydrolysis of amide bonds is 350 500 years at room temperature and pH 4 8. Clearly, efficient methods of cleavage are needed. Despite their great catalytic power and selectivity to sequence, proteinases have some disadvantages. Peptides 420,423,424,426 an(j proteins428 429 can be hydrolytically cleaved near histidine and methionine residues with several palladium(II) aqua complexes, often with catalytic turnover. 

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