When we observe a cell under a microscope or its electrical or metabolic activity, in essence, we are watching proteins. Proteins constitute the vast majority of a cell's dry mass. In addition to their role as the cell's structural components, they are responsible for the vast majority of the processes that occur within the cell. Proteins that operate as enzymes are what furnish a cell's interior with its complex molecular surfaces, which in turn catalyze the cell's myriad of chemical reactions. Protein channels and pumps that are anchored in the plasma membrane control how small molecules enter and leave the cell. These channels and pumps are responsible for regulating the transport of small molecules. Other proteins either work as integrators of signals or as messengers that transmit groups of signals from the plasma membrane to the nucleus of the cell. Some, like kinesin, are responsible for moving organelles around the cytoplasm, while others, like topoisomerase, are able to unwind DNA molecules that have become knotted. Still other molecules act as small molecular motors that move about the cell. Other proteins that have specific activities serve as antigens, poisons, hormones, antifreeze chemicals, elastic fibers, ropes, or luminous sources. They can also be ropes and elastic fibers. Before we can even begin to expect to comprehend how genes work, how muscles contract, how nerves transfer electricity, how embryos develop, or how our bodies function, we have to first get a solid understanding of proteins.

Proteins are by far the most complicated molecules that science is aware of in terms of both their structural makeup and their functions. Given that the structure and chemistry of each protein have been evolving and being fine-tuned over the course of billions of years of evolutionary history, this finding may not come as much of a surprise. The theoretical calculations of population geneticists show that over the course of evolutionary time periods, an unexpectedly small selective advantage is sufficient to induce a randomly changed protein sequence to propagate through a population of organisms. This was discovered by population geneticists. The amazing plasticity of proteins may even seem incredible to those who are quite knowledgeable in the field. In this part, we'll look at how the location of each amino acid in the long chain of amino acids that make up a protein impacts the three-dimensional form of the protein. Proteins are made up of a long string of amino acids. In the following sections of this chapter, we will use the knowledge that we have gained about the structure of proteins at the atomic level to demonstrate how the precise shape of each protein molecule affects the function that it performs inside of a cell.

There are 20 different amino acids that can be found in proteins. These amino acids are directly written for in the DNA of an organism and have a variety of chemical properties. In order to create a protein molecule, these amino acids are linked to one another in a linear fashion via covalent peptide bonds. The resulting structure looks like a long, straight chain. Proteins can also be referred to by their more general name, polypeptides. Each form of protein in a cell has its own unique sequence of amino acids, and there are thousands of different kinds of proteins that can be found in a single cell. The sequence of atoms that is repeated all the way through the middle of a chain of polypeptides is known as the polypeptide backbone. To this repeating chain are attached the 20 distinct amino acid side chains. These side chains do not participate in the creation of peptide bonds; rather, they are responsible for endowing each amino acid with its own set of characteristics. The polarity of these side chains can range from nonpolar to hydrophobic (which literally translates to "water-fearing"), and they can be positively or negatively charged, as well as easily form covalent bonds. The manner in which the protein chain folds is determined in part by the myriad of sets of weak noncovalent connections that form between the various protein chain segments. These involve atoms not just in the side chains of the amino acids but also in the atoms that make up the backbone of the polypeptide. Van der Waals attractions, electrostatic interactions, and hydrogen bonding are the three categories that can be used to classify these weak linkages.

The typical covalent bonds that form biological molecules are thirty-to-three hundred times weaker than the noncovalent connections that are made individually. Nevertheless, the two parts of a polypeptide chain can be kept firmly together by a multitude of weak bonds that operate in parallel with one another. The overall strength of a large number of these noncovalent links is what determines the degree of stability that may be achieved by each different folded shape. A substantial role is also played, along with three other weak forces, by the hydrophobic clustering force when it comes to the process of determining the structure of a protein. In an environment containing water, hydrophobic molecules, and in particular the nonpolar side chains of certain amino acids, tend to crowd together in order to lessen the amount of disruption that they cause to the hydrogen-bonded network formed by water molecules. Because of this, the proportion of polar to nonpolar amino acids in a protein is one of the most important factors that determines how that protein will fold. The nonpolar (hydrophobic) side chains of amino acids like phenylalanine, leucine, valine, and tryptophan prefer to concentrate inside the molecule of a protein. This is the case because these amino acids are part of a polypeptide (just as hydrophobic oil droplets coalesce in water to form one large droplet). They are able to avoid coming into contact with the water since this process takes place within a cell. On the other hand, polar groups, such as those found in arginine, glutamine, and histidine, have a tendency to cluster close to the edge of the molecule, which is where they are able to form hydrogen bonds with water and other polar molecules.

As a consequence of all of these interactions, the majority of proteins possess a three-dimensional structure that is determined by the order in which the amino acids in their chain are arranged. The final folded configuration of every polypeptide chain, also known as its conformation, is frequently the one that has the lowest free energy. In order to examine protein folding in a test tube, biologists utilized proteins that were extremely pure. When a folded protein chain is subjected to certain solvents that disrupt the noncovalent connections that hold the chain together in its folded state, the protein will denature or unfold. During the course of this treatment, the protein undergoes a transformation that results in it being transformed into a flexible polypeptide chain that has lost its original shape. When the solvent that caused the protein to become denaturized is removed, the protein will frequently refold or renature into its original form on its own. This finding indicates that the sequence of amino acids contains all of the information necessary to describe the three-dimensional shape of a protein, which is critical for gaining an understanding of cell biology.

The vast majority of proteins can only assume one stable shape after folding. The structure of the protein shifts subtly as a result of its interactions with the other molecules in the cell. This change in form is frequently essential to the function of the protein, as we will see in a bit more detail later. Even while a protein chain is capable of folding into the correct shape even without the assistance of other proteins, the process of protein folding is typically facilitated in a living cell by specialized proteins known as molecular chaperones. Molecular chaperones are proteins that bind to polypeptide chains that have only partially folded and then assist in moving the chains farther along the folding pathway that uses the least amount of energy. In the cytoplasm, chaperones play a vital role in preventing temporarily exposed hydrophobic regions of newly formed protein chains from forming protein aggregates by associating with one another. However, the final three-dimensional form of the protein is still determined by the amino acid sequence; chaperones merely make it more likely that the protein will reach its folded state.

The majority of proteins can range in length anywhere from 50 to 2000 amino acids, but proteins can take on a wide variety of shapes. Large proteins are typically composed of a number of separate protein domains, which are structural units that fold to a large extent independently of one another. Even a relatively simple domain can have a complex structure; consequently, it is common practice to employ multiple representations, each of which focuses on a distinct property in order to enhance comprehension.