Peptides defined

High-resolution crystal structures of MDM2 complexed with p53 peptides defined the interaction in detail, revealing that the MDM2-p53 interface has a well-defined, relatively compact binding pocket in MDM2, which suggested that for this particular... 

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. 

Most reactions in cells are carried out by enzymes [1], In many instances the rates of enzyme-catalysed reactions are enhanced by a factor of a million. A significantly large fraction of all known enzymes are proteins which are made from twenty naturally occurring amino acids. The amino acids are linked by peptide bonds to fonn polypeptide chains. The primary sequence of a protein specifies the linear order in which the amino acids are linked. To carry out the catalytic activity the linear sequence has to fold to a well defined tliree-dimensional (3D) stmcture. In cells only a relatively small fraction of proteins require assistance from chaperones (helper proteins) [2]. Even in the complicated cellular environment most proteins fold spontaneously upon synthesis. The detennination of the 3D folded stmcture from the one-dimensional primary sequence is the most popular protein folding problem. 

An interesting approach has recently been chosen in the MBO(N)D program ([Moldyn 1997]). Structural elements of different size varying from individual peptide planes up to protein domains can be defined to be rigid. During an atomistic molecular dynamics simulation, all fast motion orthogonal to the lowest normal modes is removed. This allows use of ca. 20 times longer time steps than in standard simulations. 

The free energy differences obtained from our constrained simulations refer to strictly specified states, defined by single points in the 14-dimensional dihedral space. Standard concepts of a molecular conformation include some region, or volume in that space, explored by thermal fluctuations around a transient equilibrium structure. To obtain the free energy differences between conformers of the unconstrained peptide, a correction for the thermodynamic state is needed. The volume of explored conformational space may be estimated from the covariance matrix of the coordinates of interest, = ((Ci [13, lOj. For each of the four selected conform-... 

Besides such textual databases that provide bibhographic information, sequence databases have attained an even more important role in biochemistry. Sequence databases are composed of amino add sequences of peptides or proteins as well as nudeotide sequences of nudeic acids. The 20 amino adds are mostly represented by a three-letter code or by one letter according to the biochemical conventions) the four nudeic adds are defined by a one-letter code. Thus the composition of a biochemical compound is searchable by text retrieval methods. 

ChemSketch has some special-purpose building functions. The peptide builder creates a line structure from the protein sequence defined with the typical three-letter abbreviations. The carbohydrate builder creates a structure from a text string description of the molecule. The nucleic acid builder creates a structure from the typical one-letter abbreviations. There is a function to clean up the shape of the structure (i.e., make bond lengths equivalent). There is also a three-dimensional optimization routine, which uses a proprietary modification of the CHARMM force field. It is possible to set the molecule line drawing mode to obey the conventions of several different publishers. 

In addition to the weU-defined opioid systems in the central nervous system, the three opioid peptides and their precursor mRNA have also been identified in peripheral tissues. ( -Endorphin is most abundant in the pituitary, where it exists in corticotroph cells with ACTH in the anterior lobe and in melanotroph cells with MSH in the intermediate lobe (59). Enkephalin and pre-pro-enkephalin mRNA have been identified in the adrenal medulla (60) and this has been the source of material for many studies of pro-enkephalin synthesis and regulation. Pre-pro-enkephalin mRNA has also been identified in the anterior and posterior lobes of the pituitary (61). mRNA for all three opioid precursors has been identified in the reproductive system (62—64). POMC... 

LDH-x is one of the best characterized antigens and its amino acid sequence is known. A synthetic peptide based on a portion of the molecule has been shown to reduce fertUity in laboratory animals. The nucleotide sequence coding for human LDH-x has been defined and engineered into an expression vector system (121). 

The basic chemical description of rare events can be written in terms of a set of phenomenological equations of motion for the time dependence of the populations of the reactant and product species [6-9]. Suppose that we are interested in the dynamics of a conformational rearrangement in a small peptide. The concentration of reactant states at time t is N-n(t), and the concentration of product states is N-pU). We assume that we can define the reactants and products as distinct macrostates that are separated by a transition state dividing surface. The transition state surface is typically the location of a significant energy barrier (see Fig. 1). 

An example is shown in Figure 7 for the case of the coil-to-helix transition. The endpoints of the calculation are an unstructured coil Tr and helix rp. Intermediate peptide structures correspond to transition intermediates defining the pathway l(r). 

I MHC-peptide complexes and those that recognize class 11 MHC-peptide complexes utilize the same set of Va and Vp genes, and the principal feature that defines the site of class 1 MHC-TCR interaction, the cleft formed by the a and az subunits of the MHC molecule, is shared by both class 1 and class... 

---