Structural Biology

  Biomolecules are too small to observe in detail, even with the most advanced light microscopes. These may include macro and micro molecules along with natural products. These may be endogenous and exogenous in nature. 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-Electron Microscopy and Nuclear Magnetic Resonance.

Computational approaches include most of the aspects of bio-informatics and are considered as a boon for structural biology. The method of molecular structure determination by experimental way is time-consuming and costly. To overcome these constraints, computational approaches like ab-initio modelling, homology modelling, advanced fold recognition and threading method are used.

This is a cost effective 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 of protein structures. Nevertheless, predicted structures are not given the same credits as their experimental counterparts.  Hybrid approach is a channel to overcome these disadvantages, by incorporating limited experimental measurements, reliable structures can be computed and unlikely predictions are eliminated. The current researches are showing great interest in this method of approach.

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.

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.

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 an catalogued manner, bioinformatics databases are used. Various databases have been created to store biological data, such as sequence databases, structure databases, signalling pathway databases.

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 modelling  constitutes all the hypothetical methods and computational procedures used to mimic the behaviour of macromolecules. These techniques are used in diverse fields of drug design, computational chemistry, materials science and computational biology for studying macromolecular systems ranging from small to large biological systems. In order to simulate the interactions between the atoms, for further understanding of the properties, molecular simulation uses powerful techniques. Such simulations involve methods that range from very detailed quantum mechanical calculations on atoms to coarse-grained classical dynamics of large groups of molecules on a timescale of milliseconds or longer.

Molecular dynamics (MD) 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. The trajectories of atoms and molecules are commonly determined by solving them numerically using Newton’s equations of motion for a group of collaborating particles. The forces between the particles and their potential energies are calculated using inter-atomic potentials or molecular mechanics force fields.

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. The main methods available for drug design are structure based drug design and ligand based drug design.

The main focus of a structural biologist is protein structure determination and drug design. Protein plays an important role in human body. Living things would not exist without proteins. The proteins are usually involved in all forms of expressions of the living organism. Most of the proteins are evolved in providing structure to the cell while the others tend to bin and carry vital molecules all through the body. Some proteins are involved in biochemical reactions in the body which are termed as enzymes. Others are involved in muscle contractions and immunity. Structure determination of proteins has always been a challenging filed. The complex areas in the field include viruses, pathogens, membrane proteins and signalling pathways. Novel progressions are being done in the arenas of nano-patternig and multi-scale modelling of cell signalling proteins.

The main aim of integrating structural biology data into cancer research is to design and discover novel and effective drugs to cure the diseases. Structural biology combined with molecular modelling mainly aims at drug designing. Consequently, a number of Structural Biologists are conducting cancer research, to speed-up the process of understanding the mechanism of biomolecules in order to improve the newer cancer therapies.

Structural biology aims at understanding biomolecules at atomic level. All aspects in structural biology research seem to be complex. Research methods have proved to be successful in solving many of the complexities such as protein structure determination, functional annotations and drug designing. Though protein structures are solved on a large scale, the gap between available sequence data and structure data is enormous. Bridging this gap is one of the main challenges.

Structural biology is one of the progressing fields. In the course of time many developments have been taking place. 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 proteins.