Acid sequence

Modern methods of amino-acid and peptide analysis, have enabled the complete amino-acid sequence of a number of proteins to be worked out. The grosser structure can be determined by X-ray diffraction procedures. Proteins have molecular weights ranging from about 6 000 000 to 5 000 (although the dividing line between a protein and a peptide is ill defined). Edible proteins can be produced from petroleum and nutrients under fermentation. 

Williams J G K 1997 Single-molecule detection of specific nucleic acid sequences in unamplified genomic DNA Anal. Chem. 69 3915-20... 

Circular dicliroism has been a useful servant to tire biophysical chemist since it allows tire non-invasive detennination of secondary stmcture (a-helices and P-sheets) in dissolved biopolymers. Due to tire dissymmetry of tliese stmctures (containing chiral centres) tliey are biaxial and show circular birefringence. Circular dicliroism is tlie Kramers-Kronig transfonnation of tlie resulting optical rotatory dispersion. The spectral window useful for distinguishing between a-helices and so on lies in tlie region 200-250 nm and hence is masked by certain salts. The metliod as usually applied is only semi-quantitative, since tlie measured optical rotations also depend on tlie exact amino acid sequence. 

Biological infonnation is also concerned witli tire analysis of biological messages and tlieir import. The fundamental premise of tire protein-folding problem section C2.14.2.2 is tliat tire full tliree-dimensional arrangement of tire protein molecule can be predicted, given only tire amino acid sequence, together witli tire solvent composition, temperature and pressure. One test of tire validity of tliis premise is to compare tire infonnation content of tire sequence witli tire infonnation contained in tire stmcture [169]. The fonner can be obtained from Shannon s fonnula ... 

The protein folding problem is the task of understanding and predicting how the information coded in the amino acid sequence of proteins at the time of their formation translates into the 3-dimensional structure of the biologically active protein. A thorough recent survey of the problems involved from a mathematical point of view is given by Neumaier [22]. 

The forces in a protein molecule are modeled by the gradient of the potential energy V(s, x) in dependence on a vector s encoding the amino acid sequence of the molecule and a vector x containing the Cartesian coordinates of all essential atoms of a molecule. In an equilibrium state x, the forces (s, x) vanish, so x is stationary and for stability reasons we must have a local minimizer. The most stable equilibrium state of a molecule is usually the... 

EMBL (European Molecular Biology Laboratory) [33] is a nucleotide sequence database provided from the online host EBl. Release 73 (December, 2002) consists of over 20 million nucleotide sequences with more than 28 billion nucleotides. The information includes sequence name, species, sequence length, promoter, taxonomy, and nucleic acid sequence. 

The CA Registry of CAS also comprises 1.6 million protein and peptide sequences and over 21.6 milhon nudeic acid sequences from literature sources and from GenBank. 

GenBank National Center for Biotechnology Information, USA nucleic acid sequence biblio., sub- stance, se- quence 22 mio sequences 28 billion bases journals, author submis- sions STN online daily www.ncbi.nlm.- nih.gov... 

Example Molecular dynamics simulations of selected portions of proteins can demonstrate the motion of an amino acid sequence while fixing the terminal residues. These simulations can probe the motion of an alpha helix, keeping the ends restrained, as occurs n atiirally m transmembrane proteins. You can also investigate the conformations of loops with fixed endpoints. 

Chou P Y and G D Fasman 1978. Prediction of the Secondary Structure of Proteins from Tlieir Amino Acid Sequence. Advances in Enzymology 47 45-148. 

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. 

The structures of higher peptides follow in an analogous fashion Figure 27 7 gives the structural formula and ammo acid sequence of a naturally occurring pentapeptide... 

What IS the ammo acid sequence (using three letter abbrevia ]... 

There are several levels of pepfide sfrucfure The primary structure is the ammo acid sequence plus any disulfide links With the 20 ammo acids of Table 27 1 as building blocks 20 dipeptides 20 tripeptides 20" tetrapeptides and so on are possible Given a peptide of unknown structure how do we determine its ammo acid sequence" ... 

Sanger was a corecipient of a second Nobel Prize in 1980 for devising methods for sequencing nucleic acids Sanger s strategy for nucleic acid sequencing will be described in Section 28 14... 

Organize the information so that the ammo acid sequences of small fragments can be overlapped to reveal the full sequence... 

Digestion of the tetrapeptide of Problem 27 13 with chy motrypsin gave a dipeptide that on ammo acid analysis gave phenylalanine and valine in equimolar amounts What ammo acid sequences are possible for the tetrapeptide ... 

An amino acid sequence is ambiguous unless we know the direction m which to read It—left to right or right to left We need to know which end is the N terminus and which IS the C terminus As we saw m the preceding section carboxypeptidase catalyzed hydrolysis cleaves the C terminal ammo acid and so can be used to identify it What about the N terminus ... 

Insulin has 51 ammo acids divided between two chains One of these the A chain has 21 ammo acids the other the B chain has 30 The A and B chains are joined by disul fide bonds between cysteine residues (Cys Cys) Figure 27 10 shows some of the infor matron that defines the ammo acid sequence of the B chain... 

The peptide shown m green was isolated by trypsin catalyzed hydrolysis and has an ammo acid sequence that completes the remaining overlaps... 

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