Bioinformatics lecture 3+4 Bi4999en

Protein synthesis involves transcription (DNA to RNA), splicing (RNA to mRNA), translation (mRNA to protein), and post-translational modifications (protein to mature protein).

Databases that store protein sequences, often with annotations and cross-references to other information. Types include generalist (like UniProtKB) and specialist databases (like WormBase) with different scopes.

A central repository of protein sequences and functional information, known for detailed and quality annotations.

Multiple databases hold protein sequences, categorized by scope (e.g., general or specific organism) and content (e.g., primary sequences and derived motifs).

The process of copying DNA information into RNA, a crucial step in protein synthesis.

Converting mRNA information into a protein chain.

The step in protein synthesis where non-coding parts of RNA are removed to create mature mRNA.

Proteins have different structural levels, with primary structure being the amino acid sequence.

Methods used to compare similarities between different protein sequences.

A method for measuring protein similarity where 1 indicates identical amino acids and 0 otherwise.

Methods for measuring protein similarity that consider the probability of amino acid substitutions.

A substitution model derived from observed mutations, useful for identifying evolutionary relationships among protein sequences.

A unit of evolutionary time, where 1 PAM signifies the time needed for one-hundredth of the amino acids to mutate.

The degree of difference between two sequences, often measured by PAM (Point Accepted Mutation) units.

A negative score given for introducing gaps in sequence alignments, to promote biologically meaningful alignments.

A substitution matrix that targets the limit of reliably inferring homology where it gets too distant.

Substitution matrices based on aligned fragments of conserved protein blocks (BLOCKS database).

A PAM matrix derived from the comparison of similar protein that represents one amino acid difference in 100 amino acid sequences.

A BLOSUM matrix derived from sequences clustered at 62% or greater identity.

Conserved fragments found in proteins that align well suggesting that mutations have been kept from a common ancestor.

A measure of how well a model fits experimental data.

A more reliable measure of model quality than R-factor.

Different shapes a side chain in a protein can take.

Assessing if a protein structure is reliable based on various checks.

Checking for quality of a structure created by Nuclear Magnetic Resonance.

Process of checking protein or nucleic acid structures for accuracy and reliability.

Indicate the mobility or flexibility of atoms in a protein structure.

Tools used for validating and improving NMR protein structures.

A file format storing atomic coordinates, chemical features, experimental details, and structural features of molecules, such as protein structures. Includes secondary structure, hydrogen bonds, biological assemblies, and active sites.

Widely used by many tools, easy to read & use, making it suitable for accessing individual molecular structures.

Inconsistent information between entries and within an entry (e.g., differing residue numbering), not good for extracting structured data programmatically. Data item size limitations exist, unsuitable for large or complex molecular structures.

Macromolecular Crystallographic Information File; a format designed for increasingly complex molecular data. Uses tags to explicitly assign and link information, improving data consistency.

Easily parsed by software, consistent data across the database making it suitable for large-scale analysis and comparison.

Not easily read by humans, and often not supported by visualisation tools or software.

Ensuring uniformity and accuracy of data across entire data sets. Important in analyzing many structures.

Restrictions on the amount of data that can be stored in a database. This can limit the analysis of large structures, necessitating the division of structures into smaller components if stored in a format like PDB.

A 2D graph showing the distribution of angles in a protein's backbone. It helps assess the quality of protein structures by revealing allowed and disallowed regions for the angles.

Areas on the Ramachandran plot where protein backbone angles are highly unlikely or impossible, indicating potential errors in the structure.

Unfavorable interactions between atoms in a protein structure, often detected by comparing distances to van der Waals radii.

A measure of the strength of hydrogen bonds within a protein structure, indicating important interactions for stability.

Scores that evaluate how 'happy' each amino acid residue is in its local environment within a protein structure.

A database that provides pre-computed quality criteria for protein structures deposited in the Protein Data Bank (PDB).

A database that provides a summary of information about protein structures, including quality and structural features.

A measure of how well each residue in a protein structure fits its electron density, reflecting the accuracy of the structure.

The process of creating proteins from DNA instructions, involving transcription, splicing, translation, and post-translational modifications.

Databases that focus on specific protein types or conditions, such as pathways, diseases, or specific organisms.

Databases storing patterns derived from protein sequences, representing conserved features among related proteins.

Proteins have different structural levels: Primary (amino acid sequence), Secondary (alpha helices and beta sheets), Tertiary (3D shape of a single chain), and Quaternary (interactions between multiple chains).

Predicting whether a protein sequence will fold into a soluble protein in a specific expression system. This also involves predicting the likelihood of aggregation.

Identifying regions within a protein sequence that span cell membranes. These regions are crucial for proteins that interact with the cell's outer boundary.

A type of transmembrane region where the protein folds into a helical structure, passing through the membrane.

A type of transmembrane region where the protein forms a beta-barrel structure, creating a pore through the membrane.

The principle that transmembrane helices have more positively charged amino acids on the intracellular side of the membrane.

Data consistency ensures uniformity and accuracy across a dataset, allowing for reliable comparisons and analyses of multiple structures.

Some formats have limitations on the amount of data they can store, such as limited numbers of atoms or chains, restricting the storage of large and complex molecular structures.

Gaps in sequence alignments are necessary to account for insertions and deletions (indels) that occur during evolution. They allow for the alignment of sequences that have diverged over time, revealing similarities that might otherwise be missed.

Identity matrices, which simply score identical amino acids as 1 and different ones as 0, are limited in their ability to accurately reflect protein similarity. They often force the introduction of too many gaps in alignments, making it difficult to determine the true relationship between sequences.

Substitution models are a way to overcome the limitations of identity matrices by considering the probability of amino acid substitutions. They allow us to more accurately measure protein similarity by taking into account the likelihood of certain mutations occurring over time.

A method for finding the optimal alignment between two protein sequences by calculating scores for all possible alignments and choosing the one with the highest score. It uses a matrix to store scores for aligning different segments of the sequences.

A sequence alignment method that aims to align the entire length of two sequences, including gaps to maximize similarity. It involves finding the best alignment across the entire length of both sequences.

A sequence alignment method that identifies regions of high similarity within two sequences, finding the best matching segments even if the sequences are not overall very similar. It seeks out the most similar sections within the sequences.

A method for efficiently comparing protein sequences by identifying short, non-overlapping sequences (words) within the target sequence, and finding matching words in the query sequence. This method uses matching words to define regions for further analysis and alignment.

Computational methods that use approximations and simplifying assumptions to find solutions quickly. They are often used for large-scale comparisons of protein sequences, but may not guarantee the best solution.

A method for aligning multiple protein sequences by first aligning the most similar pairs, and then gradually adding less similar sequences to the alignment. This build-up approach helps to find relationships between multiple sequences.

Databases store and organize a vast amount of information about protein structures (3D models) and sequences, aiding researchers in understanding protein function and predicting their structures.

A comprehensive database that houses protein sequences from various organisms, including detailed annotations and cross-references to other databases.

Incorporating evolutionary information, such as sequence alignments and mutation rates, improves the accuracy of predictions because it provides insights into the relationships between sequences and how they have changed over time.

It compares protein sequences, identifying similarities and differences to understand biological functions and evolutionary relationships.

Variations in protein sequences that make an individual better adapted to its environment are more likely to be passed down, leading to evolution and the development of new protein functions.

A substitution matrix that measures the likelihood of amino acid substitutions based on evolutionary time.

BLOSUM matrices are based on aligned fragments of conserved protein blocks, while PAM matrices use observed mutations.

It assesses the quality and reliability of predicted or experimentally determined protein structures by checking for errors and inconsistencies.

The specific task a protein performs. This is determined by the protein's 3D structure.

Changes in a protein's sequence (mutations) lead to changes in its 3D structure. These structural changes can affect its function, impacting the organism's survival and adaptation.

Proteins that share a common ancestor. This means they share similar sequences and structures, suggesting they perform similar or related functions.

This principle states that a protein's sequence determines its 3D structure, which in turn determines its function.

Environmental factors that favor certain traits, leading to the survival and reproduction of organisms with advantageous adaptations.

A change in an organism's traits over time that allows it to better survive and reproduce in a specific environment.

The gradual process of change in living organisms over generations due to factors like mutations and environmental pressures.

The variation in traits within a population of organisms, which allows for adaptation and evolution.

Protein sequence databases can be divided into two primary categories: generalist databases, which store sequences from any source, and specialist databases, which focus on specific conditions, such as biological pathways, diseases, or organisms.

UniProtKB is a central repository for protein sequences and their related information. It's a collaboration between the European Bioinformatics Institute (EBI), the Swiss Institute of Bioinformatics, and the Protein Information Resource.

These databases store patterns derived from primary protein sequences, representing conserved features found in families of related proteins. They offer a way to understand protein functions by analyzing recurring patterns.

Protein synthesis involves four key steps: transcription, in which DNA is copied into RNA; splicing, where non-coding parts of RNA are removed; translation, where RNA is used to build a protein chain; and post-translational modifications, where the protein is further processed to become functional.

Proteins have four levels of structure: primary structure refers to the amino acid sequence; secondary structure describes local folds like alpha-helices and beta-sheets; tertiary structure is the 3D shape of a single protein chain; and quaternary structure involves the arrangement of multiple protein chains.

Substitution models are used in sequence alignment to account for amino acid substitutions that occur during evolution. They provide a more refined way to measure protein similarity than simple identity matrices.

Global alignment attempts to align the entire length of two sequences, while local alignment focuses on finding regions of high similarity within the sequences. Global alignment seeks overall similarity, while local alignment identifies best matching segments.

The study of how protein sequences change over time due to mutations and natural selection. It helps us understand the relationships between different species and how proteins evolved.

Two proteins are homologous if they share a common ancestor. This means they originated from the same gene and have been modified over time.

The challenge of accurately labeling protein sequences with their functions. There are often many unknowns, making it difficult to assign the right function to a protein.

A table that assigns scores to different pairs of amino acids, reflecting the likelihood of one amino acid being replaced by another during evolution.

A method used to solve complex problems by breaking them down into smaller, overlapping subproblems. Applied to sequence alignment, it helps find the best alignment between two sequences.

A method for finding the best alignment between two sequences by calculating scores for all possible alignments and choosing the one with the highest score.

An efficient method for comparing sequences by identifying short, non-overlapping sequences (words) and finding matching words.

A method for measuring protein similarity that considers the probability of amino acid substitutions, taking into account the likelihood of mutations over time.

A collaboration of three organizations (RCSB PDB, PDBe, and PDBj) that manages and distributes the Protein Data Bank (PDB) archive, a database containing 3D structures of biomolecules.

The PDB archive is freely available to the public through the RCSB PDB, PDBe, and PDBj websites. Data is updated weekly and can be accessed via FTP or web interfaces.

The process of evaluating the accuracy and reliability of protein structures, ensuring their suitability for research and applications.

Errors in protein structures that stem from fundamental flaws in the modeling process, often due to limitations in experimental data or interpretation.

Errors in protein structures that occur randomly due to limitations in experimental data or the inherent nature of protein dynamics.

A type of systematic error where the protein chain is incorrectly traced through the electron density map, leading to a distorted structure.

A type of systematic error where the protein chain is shifted by one or more residues in the electron density map, leading to an incorrect structure.

A significant error in protein structure where the overall 3D shape is completely wrong.