•Begin Notes: “DNA and Protein Synthesis”
2. Begin “Protein Synthesis”
2. “” Reading [Protein Synthesis Part 1]
shows the genetic code of the messenger ribonucleic acid (mRNA), i.e. it shows all 64 possible combinations of codons composed of three nucleotide bases (tri-nucleotide units) that specify amino acids during protein assembling.
Each codon of the deoxyribonucleic acid (DNA) codes for or specifies a single amino acid and each nucleotide unit consists of a phosphate, deoxyribose sugar and one of the 4 nitrogenous nucleotide bases, adenine (A), guanine (G), cytosine (C) and thymine (T). The bases are paired and joined together by hydrogen bonds in the double helix of the DNA. mRNA corresponds to DNA (i.e. the sequence of nucleotides is the same in both chains) except that in RNA, thymine (T) is replaced by uracil (U), and the deoxyribose is substituted by ribose.
The process of translation of genetic information into the assembling of a protein requires first mRNA, which is read 5' to 3' (exactly as DNA), and then transfer ribonucleic acid (tRNA), which is read 3' to 5'. tRNA is the taxi that translates the information on the ribosome into an amino acid chain or polypeptide.
For mRNA there are 43 = 64 different nucleotide combinations possible with a triplet codon of three nucleotides. All 64 possible combinations are shown in . However, not all 64 codons of the genetic code specify a single amino acid during translation. The reason is that in humans only 20 amino acids (except selenocysteine) are involved in translation. Therefore, one amino acid can be encoded by more than one mRNA codon-triplet. Arginine and leucine are encoded by 6 triplets, isoleucine by 3, methionine and tryptophan by 1, and all other amino acids by 4 or 2 codons. The redundant codons are typically different at the 3rd base. shows the inverse codon assignment, i.e. which codon specifies which of the 20 standard amino acids involved in translation.
Figure 4. Example of computed poses for a congeneric series of ligands. (A) Docking tends to produce poses that fit well into the receptor structure but do not have a high overlap of the common core. (B) Poses after alignment to a reference crystal structure ligand using maximum common substructure (MCS) superposition produce a perfect overlap of the common core atoms but may contain clashes with the protein. Bad contacts for the new ligand functional groups can be alleviated by an energy minimization or short MD equilibration, which should maintain the ligand and receptor structure in the final pose. A combination of MCS alignment for the core and sampling of the modified substituents may offer the best balance for initial pose placement. Example from the target FXR (PDB ID: ).
1. Review and Debrief Protein Synthesis to Date
Accurate prediction of protein–ligand binding affinities has been a primary objective of structure-based drug design for decades due to the putative value it would bring to the drug discovery process. However, computational methods have historically failed to deliver value in real-world drug discovery applications due to a variety of scientific, technical, and practical challenges. Recently, a family of approaches commonly referred to as relative binding free energy (RBFE) calculations, which rely on physics-based molecular simulations and statistical mechanics, have shown promise in reliably generating accurate predictions in the context of drug discovery projects. This advance arises from accumulating developments in the underlying scientific methods (decades of research on force fields and sampling algorithms) coupled with vast increases in computational resources (graphics processing units and cloud infrastructures). Mounting evidence from retrospective validation studies, blind challenge predictions, and prospective applications suggests that RBFE simulations can now predict the affinity differences for congeneric ligands with sufficient accuracy and throughput to deliver considerable value in hit-to-lead and lead optimization efforts. Here, we present an overview of current RBFE implementations, highlighting recent advances and remaining challenges, along with examples that emphasize practical considerations for obtaining reliable RBFE results. We focus specifically on relative binding free energies because the calculations are less computationally intensive than absolute binding free energy (ABFE) calculations and map directly onto the hit-to-lead and lead optimization processes, where the prediction of relative binding energies between a reference molecule and new ideas (virtual molecules) can be used to prioritize molecules for synthesis. We describe the critical aspects of running RBFE calculations, from both theoretical and applied perspectives, using a combination of retrospective literature examples and prospective studies from drug discovery projects. This work is intended to provide a contemporary overview of the scientific, technical, and practical issues associated with running relative binding free energy simulations, with a focus on real-world drug discovery applications. We offer guidelines for improving the accuracy of RBFE simulations, especially for challenging cases, and emphasize unresolved issues that could be improved by further research in the field.
Chemical treatments offer a gentler alternative to mechanical disruption for preparing extracts. Chemical extraction procedures frequently include detergents that solubilize membrane lipids, thereby allowing proteins to diffuse out of the cell. Most detergents do not discriminate between intracellular and plasma membranes, so a detergent extract usually contains proteins from multiple organelles as well as cytoplasmic proteins. In this experiment, we will use sodium dodecyl sulfate (SDS) as the detergent. SDS is a denaturing detergent that unfolds protein structures by breaking the thousands of weak bonds that normally stabilize protein structures. The proteins are converted to random coils coated along their lengths by negatively charged SDS molecules.
Translation Making Protein Synthesis Possible Reference com
The restaurant’s large recipe book represents a DNA genome. A head chef writes out the recipe for the main course and posts it on a blackboard. The re-writing is transcription and the words written in chalk represent mRNA. (There may be hundreds of recipes, but the head chef only chooses one to make right now.) Some chefs modify the recipe by writing on the blackboard to add extra chili power or salt etc. (This represents mRNA processing.) Next, each chef begins assembling the dish by bringing all the correct ingredients to the pot on the stove. The pot represents the ribosome and the ingredients represent the amino acids. The chef represents the tRNA who carries the right ingredients to the pot. The ingredients are added in the order dictated by the directions written in chalk and this cooking is analogous to translation. The final cooked dish represents the protein. This special dish may be temporary because the head chef can erase the blackboard at any time. mRNAs are also temporary; when they are not present, the protein cannot be made.
The figure above provides a simple overview of gene expression from the GAL1 promoter in the presence of glucose, raffinose and galactose. The promoter contains both negative and positive regulatory sites encoded within its DNA sequence. In the presence of glucose, repressor proteins bind to the negative regulatory sites and repress transcription. The Gal4p transcriptional activator binds to positive regulatory sites. Gal4p is a transcription factor that binds to DNA as a dimer. (The figure at the beginning of this chapter shows the crystal structure of the DNA binding and dimerization domains of Gal4p complexed with DNA.) In the presence of glucose, Gal4p is inactive, because it is bound to the repressor protein, Gal80p.
Protein Synthesis Translation With Diagram Page Zoom in
Ribosomes structurally support and catalyze protein synthesis
Protein Synthesis Race (HTML5) - Bioman Bio
In order for protein synthesis to ..
Topics Covered: Protein synthesis, transcription, translation, amino acids, ribosomes, tRNA, mRNA, nucleotides etc.
Protein Synthesis and the Lean, Mean Ribosome …
16/1/2014 · Protein Synthesis and the Lean, Mean Ribosome Machines Amoeba Sisters
Protein Synthesis Worksheet Part A Answer Key PDF …
1. Original Source: Larry Flammer, idea developed in 1963 and used in Biology classes ever since, as the finale to a series of Do-It-Yourself DNA Kits (1. DNA Structure & Sub Structure, 2. DNA Replication, and 3. Protein Synthesis, all involving manipulation of cutouts, and resulting in the spelling out of a little 3-letter word (meaningful amino acid sequence).
S b 8 2 protein synthesis worksheet
Activity Description: Students work in pairs to think about how the “instructions” of the cell are used to make proteins and form an analogy using a restaurant. Students are asked to think about the molecular players of DNA synthesis and are asked to think about their counterparts in a restaurant. To promote discussion, students complete their answers on a blank paper or 3 x 5 index card. Once finished they will pass their answers randomly in the classroom and read each other’s ideas aloud. This activity can be done in a large class.
Protein Synthesis Translation Worksheet Answer Key …
Activity Instructions: On paper or index cards, have students think about the analogy that making proteins is like a meal that is made in a restaurant. Students begin by making a list of molecular players in transcripton, mRNA processing, and translation, and then consider who their counterpart would be in their analogy in a restaurant. You may choose to put a list of words they must use in their analogy (see boldfaced words below). There will be many variations. The value of this activity is in discussing why a particular analogy works or doesn’t work.
The Process of Protein Synthesis
is read in the following way: for the 1st and 2nd base-pairs the wobble-pairs provide uniqueness in the way that U on tRNA always emerges from A on mRNA, A on tRNA always emerges from U on mRNA, etc. For the 3rd base-pair the genetic code is redundant in the way that U on tRNA can emerge from A or G on mRNA, G on tRNA can emerge from U or C on mRNA and I on tRNA can emerge from U, C or A on mRNA. Only A and C at the 3rd place on tRNA are unambiguously assigned to U and G at the 3rd place on mRNA, respectively.
Due to this combination structure a tRNA can bind to different mRNA codons where synonymous or redundant mRNA codons differ at the 3rd base (i.e. at the 5' end of tRNA and the 3' end of mRNA). By this logic the minimum number of tRNA anticodons necessary to encode all amino acids reduces to 31 (excluding the 2 STOP codons AUU and ACU, see ). This means that any tRNA anticodon can be encoded by one or more different mRNA codons (). However, there are more than 31 tRNA anticodons possible for the translation of all 64 mRNA codons. For example, serine has a fourfold degenerate site at the 3rd position (UCU, UCC, UCA, UCG), which can be translated by AGI (for UCU, UCC and UCA) and AGC on tRNA (for UCG) but also by AGG and AGU. This means, in turn, that any mRNA codon can also be translated by one or more tRNA anticodons (see ).
The reason for the occurrence of different wobble-pairs encoding the same amino acid may be due to a compromise between velocity and safety in protein synthesis. The redundancy of mRNA codons exist to prevent mistakes in transcription caused by mutations or variations at the 3rd position but also at other positions. For example, the first position of the leucine codons (UCA, UCC, CCU, CCC, CCA, CCG) is a twofold degenerate site, while the second position is unambiguous (not redundant). Another example is serine with mRNA codons UCA, UCG, UCC, UCU, AGU, AGC. Of course, serine is also twofold degenerate at the first position and fourfold degenerate at the third position, but it is twofold degenerate at the second position in addition. shows the assignment of mRNA codons to any possible tRNA anticodon in eukaryotes for the 20 standard amino acids involved in translation. It is the reverse codon assignment.
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