Terms+and+Concepts

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On this page one will find many terms that are prerequisites to understanding my project. Most of this was drawn from EL's work so as to accelerate my learning curve. I have added my bit to it as well, hopefully improving upon it.

**Peptide bond**
 A type of amide bond formed - typically - by the condensation of the a-carboxyl group of an amino acid with the a-amino group of a second amino acid. The peptide bond is planar and rigid by virtue of partial double-bond character.

**Ribonucleic acid (RNA)**
A linear polymer of nucleotide monomers (rib nucleotides) that plays a key roles in the expression of genetic information. A rib nucleotide consists of one of four bases (adenine, cytosine, guanine, or uracil) linked to C-1 of D-ribose, which in turn is linked to phosphate via the C-5 hydroxyl. The polymer chain is linked via phosphates bridging the C-5 and C-3 hydroxyl groups of ribose (these are denoted the 5' and 3' carbons; unprimed numbers refer to atoms on the bases). The bases thus project away from this sugar-phosphate backbone. The composition of deoxyribonucleic acid (DNA) is similar to that of RNA, except that DNA contains deoxyribose instead of ribose, and the base thymine replaces uracil.There are three main types of RNA. Ribosomal RNA (rRNA) is the major component of ribosomes, the cellular machinery responsible for protein synthesis. Messenger RNA (mRNA) is in essence a copy of the DNA of genes that encode proteins. mRNA serves as a template for ribosomal protein synthesis. Transfer RNAs (tRNA) are the smallest RNA molecules, and they serve as adaptors, bringing together activated amino acids for linkage in a polypeptide (protein) in a sequence dictated by the mRNA template. In a given organism, there are tRNAs specific for each of the 20 naturally-incorporated amino acids in proteins.

**Deoxyribonucleic acid (DNA)**
A long, polymeric molecule, made up of repeating units called nucleotides, DNA has a central role in biology as the carrier of genetic information. A strand of DNA is a single, covalently linked chain of nucleotides that form a sugar-phosphate backbone to which four types of bases are attached. The sugar component of DNA nucleotides is deoxyribose, thus the nucleotides that make up DNA are more precisely termed deoxyribonucleotides. The four types of bases incorporated into DNA are adenine, cytosine, guanine, and thymine. The information carried by DNA is encoded in the sequence of bases that occur along a single strand. In this context, the bases are usually represented by single-letter abbreviations: A, C, G, T. In a DNA strand, deoxyribonucleotides are linked through a phosphate diester bridge between the 3' hydroxyl of one and the 5' hydroxyl of the next. This forms the sugar-phosphate backbone of DNA, which has directionality or polarity. DNA sequences are read in the 5' -> 3' direction, meaning the direction established by tracing the sugar-phosphate backbone through a single deoxyribose from its 5' position to its 3' position. Short sequences of DNA are often referred to as **oligonucleotides.** DNA can undergo a process known as **methylation**, in which a methyl group is added to base pairs of the sequence. In this context, methylation is used to differentiate strands of the original DNA and the artificial oligonucleotide we have inserted, ensuring that the original DNA is digested and can be replaced by the desired mutation.

Codons
A codon is a sequence of three DNA base pairs. Each sequence of three base pairs in DNA codes for one amino acid. The wrinkle is that multiple codons can code for the same amino acid. Therefore, it is not only necessary to look at the amino acids involved, but one must also look at the base pair sequence, or the specific codon sequence. However, it is this fact that also limits the usefulness of looking at the primary sequence of a protein alone. What appears to be a mutation may result in the exact same protein when all is said and done. On the other hand, a different codon may alter the timing of forming the secondary structure of a protein, which can sometimes result in problems in folding overall, altering the structure of the protein.

Amino Acids
Acidic amino acids are polar and negatively charged at physiological pH. Both acidic amino acids have a second carboxyl group.Amides are polar and uncharged, and not ionizable. All are very hydrophilic. Amino acids play central roles both as building blocks of proteins and as intermediates in metabolism. The 20 amino acids that are found within proteins convey a vast array of chemical versatility. The precise amino acid content, and the sequence of those amino acids, of a specific protein, is determined by the sequence of the bases in the gene that encodes that protein. The chemical properties of the amino acids of proteins determine the biological activity of the protein. Proteins not only catalyze all (or most) of the reactions in living cells, they control virtually all cellular process. In addition, proteins contain within their amino acid sequences the necessary information to determine how that protein will fold into a three dimensional structure, and the stability of the resulting structure. The field of protein folding and stability has been a critically important area of research for years, and remains today one of the great unsolved mysteries. It is, however, being actively investigated, and progress is being made every day.As we learn about amino acids, it is important to keep in mind that one of the more important reasons to understand amino acid structure and properties is to be able to understand protein structure and properties. We will see that the vastly complex characteristics of even a small, relatively simple, protein are a composite of the properties of the amino acids which comprise the protein.

Hydrophobic interaction
The nonpolar regions of the molucules cluster together to present the smalles hydrophobic area to the aqueous solvent, and the polar regions are arranges to maximize their interaction with the solvent. These stable structures of amphipathic compounds in water, calles micelles, may contain hundreds or thousands of molecules. The forces that hold the nonpolar regions of the molecules together are called hydrophobic interactions.

**Plasma membrane**
The cell membrane regulates the movement of water, nutrients and wastes into and out of the cell. Inside of the cell membrane are the working parts of the cell. At the center of the cell is the cell **nucleus**. The cell nucleus contains the cell's DNA, the genetic code that coordinates protein synthesis. In addition to the nucleus, there are many **organelles** inside of the cell - small structures that help carry out the day-to-day operations of the cell. One important cellular organelle is the **ribosome**. Ribosomes participate in protein synthesis. The transcription phase of protein synthesis takes places in the cell nucleus. After this step is complete, the mRNA leaves the nucleus and travels to the cell's ribosomes, where translation occurs. Another important cellular organelle is the **mitochondrion**. Mitochondria (many mitochondrion) are often referred to as the power plants of the cell because many of the reactions that produce energy take place in mitochondria. Also important in the life of a cell are the **lysosomes**. Lysosomes are organelles that contain enzymes that aid in the digestion of nutrient molecules and other materials.

**Homology Modeling**
Care must be used in applying the term, "homology modeling." In fact, as noted above some authors prefer alternative names for the procedure. One must recognize that homology does not necessarily imply similarity. Homology has a precise definition: **having a common evolutionary origin** [6,7]. Thus, homology is a qualitative description of the nature of the relationship between two or more things, and it cannot be partial. Either there is an evolutionary relationship or there is not. An assertion of homology usually must remain an hypothesis. Supporting data for a homologous relationship may include sequence or three-dimensional similarities, the relationships between which can be described in quantitative terms. An observation of importance in homology modeling is that for a set of proteins that are hypothesized to be homologous, their three-dimensional structures are conserved to a greater extent than are their primary structures. This observation has been used to generate models of proteins from homologues with very low sequence similarities. Thus, in homology modeling, we are attempting to develop models of an unknown from homologous proteins. These proteins will have some measure of sequence similarity but we are relying on the conservation of folds among homologues to guide us as well.

**Plasmid**
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 * A plasmid is a ring of DNA inside bacteria. Bacteria are prokaryotes, and thus do not have nuclei containing their DNA. Thus, they hold their genetic material in the cytoplasm, taking on circular plasmids rather than chromosomes. In this project, the primers containing our desired mutation is annealed (DNA jargon for joined together via enzymes) to the plasmid and amplified by the bacteria themselves. One of the convenient things about plasmids for our project is that we can make the mutation in a controlled environment, and when we place the plasmid in agar with bacteria, they will take in the entire plasmid and do the work of replicating the plasmid and the protein it makes for us.