Structural biology deals with the study of the molecular structure, dynamics of biological macromolecules and how variations in the structures of molecule affect their function. Structural biology incorporates the principles of molecular biology, biochemistry and biophysics.
The majorly used methods that Structural Biologists use are:
- Macromolecular Crystallography
- Mass Spectrometry
- Nuclear Magnetic resonance spectroscopy (NMR)
- Electron Paramagnetic Resonance (EPR)
- Cryo-electron Microscopy (cryo-EM)
Molecular Biology is the branch of biology that studies the composition, structure and interactions of cellular molecules, which carry out the biological processes essential for the cells functions and maintenance. The center of attraction is where DNA creates RNA and RNA creates protein. By applying the principles of biology, chemistry, and engineering, we can create plenty of chemicals, antibodies, proteins, and enzymes in a better manner. This leads the molecular biology into various disciplines like agricultural molecular biology, medical or pharmaceutical molecular biology, industrial molecular biology and environmental molecular biology.
Structural biology is a branch of molecular biology, biochemistry, and biophysics concerned with the molecular structure of biological macromolecules. The main focus of biochemistry is to find how biological molecules give rise to the processes happening inside the living cells. Biophysics or biological physics associates with degree knowledge domain science that applies the approaches and ways of physics to review biological systems. Biophysical analysis shares vital overlap with organic chemistry, chemical science, engineering, engineering science, procedure biology, biomechanics and systems biology.
Computational Biology includes most of the aspects bioinformatics. It is the science of using biological data to develop algorithms or models to understand among various biological systems and relationships. There are approximately more than 3.3 million sequences without structure. This gap in the structural knowledge can be bridged by computation. Computational biology has become an important part of developing emerging technologies for the field of biology. Identification of suitable template of the related protein family plays a major role. The most common approaches in computational biology are ab-initio modeling, homology modeling and threading method. Among these approaches, genetic algorithm is found to be a promising co-operative computational method to solve the structure problem in reasonable time.
Genetic informatics is a branch of science which is computer-based, which emphasizes on the databases and software developmental tools. The biological phenomena are studied based on the biomolecules and their interactions which lead to a complete metabolism of the organism and in understanding the evolution of life. This helps in explaining the intrinsic cellular studies, genetic factors, genetic diseases, medications and correlation with the other evolutionary species. The databases realm within them, such that the data source of every bio-molecule thus making it easily accessed, managed and updated by the researchers.
3D Structure Determination summarizes the protein structural predictions, as a main scope for understanding and manipulating of its biochemical and cellular functions using the software tools of modern technology. This major aspect is based on computational aspects used in Bioinformatics and chemistry. Computational prediction methods, as Ab initio fragment assembly, advanced fold recognition, composite approaches, and molecular docking are explicitly applied to extend the deeper study of protein structures.
The structural biology and molecular modelling field is concerned with how various molecules in biological compounds are arranged and how the peculiarity of the arrangement affects the nature of the compound.
Molecular modeling is a scientific field of simulation of molecular systems. It represents the molecular structure numerically and simulating its behavior with the equations of quantum physics. Basically, it provides a tool to visualize 3d structure and to analyze the properties and behavior of the molecules on atomic level. It is widely used in drug designing to identify new lead compounds. Molecular dynamics deals with the study of physical movements of the atoms and molecules using computer simulation method, so it is referred to as one of the type of N-body simulation. The atoms and molecules are allowed to interact for a fixed period of time, giving a view of the dynamic evolution of the system.
Enzymes play a crucial role in signalling the cellular and metabolic pathways. Research works are going on to identify, how the enzymes function at molecular and atomic level by combining the modern biochemistry and structural biology. Techniques which are being employed to investigate enzyme structure and dynamics include X-ray crystallography, NMR, mass spectroscopy and protein chemistry, while their chemical behavior is being characterized by rapid-reaction and steady-state kinetics, calorimetry, chemical analyses, and a variety of spectroscopies.
With the increase in studies of biosciences and urge of emerging computational and experimental techniques, the application of the computational tools and expertise in the biophysics has led the way for emerging computer programming for the immense biological studies. Computer programs predict atomic, molecular properties and reaction paths for chemical reactions of biomolecules. Structural genomics emphasizes high throughput of every protein encoded by the genome determining protein structures. These methods help in scrutinizing the protein structures which are cost effective and time conservative.
The different methods in molecular biology are hemacytometer cell counter, restriction enzyme digest, DNA ligation, transfection, western blot, plasmid purification, electroporation, heat shock method, and ELISA. There are various techniques used in molecular biology, some of them are;
- Polymerase chain reaction (PCR)
- Expression cloning
- Gel electrophoresis
- Macromolecule blotting and probing
- Arrays and many More...
Viruses show different morphologies in their shapes and sizes. These are smaller in structures than the bacteria. Viruses are simple as an individual while when formed in group they are exceptionally diverse both in replication strategies and structures. The techniques which are mainly used to determine viral structures are x-ray crystallography, NMR and cryo-EM. We investigate macromolecular interactions associated with virus cell entry, genome replication, assembly, and maturation. Viruses are very simple enough that we can aspire to understand their biology at a molecular level. Our efforts are directed towards using structural information for the development of anti-viral drugs and vaccines.
Plant molecular biology is a peculiar field of science for investigating plant cells and changing them to increase the usefulness of plants in everyday life. Career areas include agriculture, food science, health care, environmental science and teaching. Plant molecular biology explores the role of certain cells, their function in plant life and methods to alter those cells to greater effect. Some of the most common traits studied are reactions to various stresses, resistance to common disease and minerals contained within the plant.
Cell biology explains the structure and organization of the organelles they contain. It includes the physiological properties, metabolic processes, signaling pathways, life cycle, and interactions with their environment. Generally, cells communicate by the release of chemical signals. They are often secreted from the cell and released into the extracellular space. Regulation of gene expression comprises a comprehensive range of mechanisms that are used by cells to regulate the production of specific gene products and is familiarly termed as gene regulation.
Sophisticated programs of gene expression are extensively observed in biology, for example to trigger developmental pathways, adapt to new food sources, or respond to environmental stimuli. Eventually the gene expressions can be adjusted, starting from transcription, initiation to post translation modification of a protein.
Molecular Microbiology inquires about centres on the bacterial cell cycle, translation direction, chromosome isolation and cell division. It Incorporates the Structure-function examination of the NusA-RNA polymerase interaction, Exploitation of the interaction of start factor with RNA sequencing and examination for unused anti-microbial advancement, Frameworks science of the model Gram positive life form Bacillus, Bacterial chromosome repair mechanisms. It points at understanding protein trade, solute transport and cell division in micro-organisms. These forms take place at the cytoplasmic film of micro-organisms, and membrane manufactured biology medication.
Genome is an important field in computational biology in the development of tools for DNA sequence information and analysis, gene mapping, genetic variation, complex trait mapping, predict protein sequence and structure. Next Generation sequencing results in large amounts of long or short DNA reads requiring assembly process to generate the complete genome sequence. In future, there are possibilities for the development and maintenance of databases of genomic, which includes new tools for annotating complex genomes to expand their utility.
Molecular genetics explains about the structure and function of genes at a molecular level and thus employs methods of both molecular biology and genetics. The study of chromosomes and gene expression of an organism can give insight into heredity, genetic variation and mutations. Molecular genetics is useful in the study of developmental biology and in understanding and treating genetic diseases. The techniques which are used in Molecular Genetics process are;
- Separation and detection
Structural bioinformatics is a structural biology studies which characterizes biomolecules and their arrangement at the molecular and atomic level. Analysis and prediction of 3D-structures of macromolecules such as proteins, RNA and DNA by computational methods has brought biological insights and global prospective. Structural bioinformatics tools have been developed, evaluated, applied to answer specific questions concerning a broad range of topics. Structural bioinformatics databases offer enormous possibilities for gathering analysis of available information about bio-macromolecules and in broadening the possibility of analysis.
Sequence analysis can be explained as a process of exposing DNA, RNA or peptide sequence to a wide range of analytical methods in order to understand its structure, function and evolution. The methods include sequence alignment, biological databases. The sequences are being compared to that of the known functions, harmoniously to understand the biology of the organism which gives the new sequence. Synergistic use of three-dimensional structures and deep sequencing is done to realize the effect of personalized medicine.
A database is an organised collection of data. As a result of enormous research which is being done in Structural biology massive data has been produced. In order to assemble the data in a catalogued manner, bioinformatics databases are used. Various databases have been created to store biological data, such as sequence databases, structure databases, signalling pathway databases, etc.
Protein data bank
Electron microscopy data bank
Protein structure classification database
Classification of structural database
Classification of protein structure
Crystallography deals with the structure and properties of crystals. It is used to determine the arrangements of atoms in the crystalline solids. Now crystallography depends on analysis of the diffraction patterns of the sample targeted by the beam of some type, mostly x-ray. The most commonly used radiations are x-ray, neutrons, and electrons. To acquire the spatial arrangement of an atom, the radiation should be of shorter wavelength.
NMR is a method used to obtain information about the structure and dynamics of proteins, nucleic acids, and their complexes. Structure determination by NMR spectroscopy consists of several phases, where each phase has a separate set of highly specialized techniques. NMR depends upon the quantum mechanical properties of a nucleus of an atom.
Mass Spectroscopy technique is used to identify the unknown compounds, determining the isotopic composition of elements in a molecule and determining the structure of a compound by observing its fragmentation. Mass Spectrometry is used in both qualitative and quantitative ways. Some of the applications are trace gas analysis, pharmacokinetics, protein characterization, space exploration, respired gas monitor and preparative mass spectrometry.
Structural Biology plays an important role in Cancer Research in order to understand the structure of cell, design and discover novel and effective drugs to cure the disease. Structural biology combined with molecular modelling mainly aims at drug designing. The biologists carry out research in order to understand the biomolecules, identify different drug targets and improvise cancer therapies.
Biomarkers include tools and technologies that aid in dynamic and powerful approach to understand the spectrum of neurological diseases in knowing the prediction, cause, diagnosis, progression, regression, or outcome of treatment of a disease.
Drug design is an innovative process to asset new medication based on the knowledge of biological target. Drug is most commonly a small molecule that inhibits or activates the function of a biomolecule, which in turn outcomes in a therapeutic benefit to the patient. Drug design commonly but not essentially relies on computational techniques. This type of modelling is often mentioned to as computer-aided drug design. Drug design that depends on the knowledge of the 3D structure of the target is known as structure-based drug design.
Proteomics is a large-scale study of proteins. Proteins have a wide variety of structures and functions in Structural and Molecular Biology. This is mainly achieved using different technologies such as x-ray crystallography and NMR spectroscopy. Molecular Medicine promotes the thoughtful of biological mechanism of disease at the cellular and molecular levels for enhanced diagnoses, treatment, and prevention of disease. Proteomics plays an important role in medical research and molecular medicine, such as in drug discovery and diagnostics, because of the link between proteins, genes and diseases and it is considered to be the next step in modern biology. Proteomics is dynamic compared to genomics because it changes constantly to reflect the cell's environment. The main objectives in the arena of proteomics are; identifying all proteins, analyse differential protein expression in different samples, characterise proteins by identifying and studying their function and cellular localisation, and recognize protein interaction networks.
Hybrid Approach is a highly cost efficient approach for determining the protein structure. The computational prediction methods, such as initiating fragment assembly, advanced fold recognition, composite approaches, and molecular docking are regularly applied in recent times to expand our understanding on protein structures. However, speculating the structures of proteins remains a confront, with congestions from both force field and conformational search. Hybrid approach is a way to overcome these disadvantages, by including the limited experimental measurements, reliable structures that can be computed, and unlikely predictions are eliminated. Hybrid approaches take advantage of data derived from a range of very different biochemical and biophysical methods.
Novel Imaging Techniques which covers the topics x-ray crystallography, NMR, powder diffractometry, mass spectroscopy, ultra-faster laser spectroscopy. Biomolecules are too small to observe in detail, even with the most advanced light microscopes. Structural biologists generally use these methods to determine the structures of identical molecules in a huge quantity at a time. Scientists use these methods to study the "real states" of the biomolecules. Some of the best methods include X-ray-Crystallography, cryo-EM, NMR and Ultra-fast laser Spectroscopy etc.
Structural biology targets aiming in comprehending the biomolecules at atomic level. Every aspect related in structural biology research seems to be complicated. The emerging research methods proved to be success in solving many complexities such as determination and functionality annotations of the protein structures in drug designing and the drug target locations. Today's science is successful in determining the protein structures which are solved on a large scale; but the gap between available sequence data and structure data is enormous. Bridging the gap is one of the main challenges for computing science.
Currently, Structural and molecular biology is one of the progressing fields. Huge numbers of solved structures have exaggerated rapidly. The field of drug design and drug discovery has been advanced. Functional annotations are another field where progressions are rapidly evolving. Alterations in order to improve the effectiveness of prevailing tools can also be noted. Remarkable advances have been made in the areas of technical imaging and advancement of hybrid methods to understand the structure and function of molecule.
- Structure determination
- Technological Advances in Existing Methods
- New and Potentially Disruptive Technologies
- Advances in Drug Design
- Advances in Tool Development
- Advances in imaging Technologies