10^th International Congress on Structural Biology October 18-19, 2018 Helsinki, Finland

Computational Approaches in Structural Biology

Computational approaches are a benefits for structural biology. Structure of molecules is determined by experimental methods which is tedious and practical. Computational biology is an interdisciplinary field that develops and applies computational methods to analyze large collections of biological data, such as genetic sequences, cell populations or protein samples, to make new predictions or discover new biology. The computational methods used include analytical methods, mathematical modeling, and simulation. It is a rapidly developing multi-disciplinary field. The systematic achievements of data made possible by genomics & proteomics technologies have created a tremendous gap between available data & their biological interpretation.

Hybrid Approaches for Structure Prediction

Structural bioinformatics is the special practical result for protein structure determination. Structural Bioinformatics is an interdisciplinary field that deals with the three-dimensional structures of biomolecules. It attempts to model and discover the basic principles underlying biological machinery at the molecular level. It is based on the hypothesis that 3D structural information of a biological system is the basic to understanding its mechanism of action and function. Structural bioinformatics combines applications of physical and chemical principles with algorithms from computational science. Major areas protein and nucleic acid 3D structure determination, prediction of protein 3D structure from sequence, protein structure validation protein structure comparison and alignment, protein and nucleic acid structure classification inferring protein function from structure, prediction of protein-ligand interaction, prediction of protein-protein interactions, development of databases.

• Hybrid of experimental methods
• NMR structures
• Hybrid of computational methods
• Determining protein complex structures
• Bottom-up integration of atomic detail crystallography
• Hybrid approaches in complementing high-resolution structural biology

Sequencing

Sequencing meets structural biology is a dedicated track to show how the recently developed methods are used to determine the structure of molecules. This approach proves itself helpful in a more efficient way. Synergistic use of three-dimensional structures and deep sequencing is done to realize the effect of the personalized medicine.  To know the order of nucleotide in small targeted genomic regions or entire genome sequencing method is utilized. Sequencing allows researchers to ask virtually any question related to the genome, transcriptome, or epigenome of an organism as it enables a wide range of application. Next-generation sequencing (NGS) method is different as for how the DNA or RNA samples are placed, and data analysis is done.

Structural Biology Databases

A biological macromolecule's function is known by the chemical and physical properties of its three‐dimensional (3D) structure. For this one should know the structure of a biomolecule which is very helpful if we want to understand the living systems and diseases. A database is a structured collection of data. In the field of structural biology enormous research is being done and as the result, massive data is being produced. In order to pile the data in an organized manner, bioinformatics databases are used. Many databases are created so that the biological data can be stored such as sequence databases, signaling database,  structure database, etc. The Protein database(PDB) which a crystallographic database is used for 3D structural data of larger biomolecules.The advancement in technologies had been reflected in the further development of the PDB and in the structural speciality and structural characteristic databases that have also evolved. In the field of structural biology, the mainly used databases are Protein Data Bank (PDB), Electron Microscopy Data Bank, Protein Structure Classification Database (CATH) and Structural Classification of Protein (SCOP).

• Classification of structural database

• Classification of protein structure

• Protein structure classification database

• Protein data bank

• Electron microscopy data bank

Signaling Biology

Cell signaling is part of any communication process that governs key activities of cells and coordinates all cell actions. The ability of cells to perceive and correctly respond to their microenvironment is the basis of development, tissue repair, and immunity, as well as normal tissue homeostasis. Errors in signaling interactions and cellular information processing are responsible for diseases such as cancer, autoimmunity, and diabetes. By understanding cell signaling, diseases may be treated more effectively and, theoretically, artificial tissues may be created the process by which a gene's information is converted into the structures and functions of a cell by a process of producing a biologically functional molecule of either protein or RNA is made.

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. Gene expression can be modulated, from transcription initiation to post-translation modification of a protein.

Molecular Modelling and Dynamics

Molecular dynamics (MD) is a computer simulation method for understanding the physical movements of atoms and molecules. The interaction between atoms and molecules is for a fixed period of time, giving a view of the dynamic evolution of the system. The molecular simulation uses powerful computers to know the interactions between atoms and to understand the properties of materials. Such simulations involve methods that range from very small quantum mechanical calculations on atoms to classical dynamics of large groups of molecules on a timescale of milliseconds or longer.

These techniques are used in various fields of drug design, computational chemistry, materials science and computational biology for knowing macromolecular systems ranging from small to large biological systems. Simplest calculations can be achieved manually, but computers are required to perform molecular modelling of the large-sized system. The common feature of molecular modeling methods is the atomistic level description of the molecular systems. This may include treating atoms as the smallest individual unit or explicitly modeling electrons of each atom. 

• Potentials In Molecular Dynamics

• Steered Molecular Dynamics

• Molecular Dynamics Algorithms

• Incorporating Molecular Dynamics 

• Design Constraints      

Drug Designing

Drug design is an inventive process to find new medication centered on the knowledge of the biological target. It is also known as also known as rational drug design.A drug is most a small molecule that inhibits or activates the function of a biomolecule, which in results into a therapeutic benefit to the patient. Drug design commonly relies on computational techniques. This type of modeling 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 structure-based drug designing also known as direct drug design involves the three-dimensional structure of a drug target interacting with small molecules is used to guide drug discovery. It represents the idea that one can see exactly how the molecules interact with its target protein.Ligand-based drug design also known as indirect drug design is an approach used in the absence of the receptor 3D information and it relies on knowledge of molecules that bind to the biological target of interest. The most important and widely used tools in ligand-based drug design involve QSAR & pharmacophore modeling.

Frontiers in Structural Biology

The main focus of a structural biologist is protein structure determination and drug design. Protein plays an important role in human body. Proteins are one of the most important parts of any biological systems. Living things would not exist without proteins as it is involved in all aspects of living things. Several proteins provide structure to cells; others tend to bind to 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 field. The complex areas in the field include viruses, pathogens, membrane proteins and signaling pathways. Novel progressions are being done in the arenas of nanopatterning and multiscale modeling of cell signaling proteins. Understanding the folding of the amino-acid chain to produce functional proteins is essential for studying cellular systems. A problem in structural bioinformatics is to determine the three-dimensional (3-D) structure of a protein when only a sequence of amino acid residues is given. These methods can be divided into four main classes: (a) first principle methods without database information; (b) first principle methods with database information; (c) fold recognition and threading methods, and (d) comparative modeling methods and sequence alignment strategies.

Structural Biology in Cancer Research

The major part of research is being carried out in the area of cancer. The main aim is to design and discover novel and effective drugs to cure the disease. Structural biology combined with molecular modeling mainly aims at drug designing. Eventually, many researchers in Structural biology carry out cancer research to extend the exploitation of molecular understanding of biomolecules in the advancement of novel cancer therapies. Cancer immunotherapy is also used which is defined as the response of immune system to reject cancer. Immunotherapies can be a better way of treating cancer. The malignant tumor cells are attacked by stimulating the immune system as these cells are responsible to exploit the fact that cancer cells often have molecules on their surface that can be detected by the tumor-associated antigens (TAAs).

• Antibody Therapy

• Cellular Immunotherapy

• Cytokine Therapy

• Combinational Immunotherapy

Structural Biology Complexity Arenas

Structural biology focuses at the atomic level for understanding the biomolecules. Most of the aspects of structural biology are complex. Researchers are proving to be successful in solving these complexities like the determination of protein structures, functional annotations and drug designing. Though structures of proteins are solved on a huge scale, the gap between available sequence data and structure data is enormous. Bridging this gap is one of the main challenges. In the current research, some of the most complex areas are protein folding, catching the complication of dynamic nanomachines and signaling networks, understanding the intrinsically disordered proteins.

• Targeting Intrinsically Disordered Proteins

• Catching the Complexity of Dynamic Nanomachines

• Bridging the Gap between Sequence Data and Structure Data

• Networks of Signaling

• Protein Folding Dynamics

Recent Advances in Structural Biology

Structural biology is one of the developing fields. In the course of time, many innovations have taken place. A large number of solved structures have amplified rapidly. The field of drug design and drug discovery has been advanced. Functional annotations are another field where progressions are being seen. Alterations, in order to improve the effectiveness of prevailing tools, can also be noted. Remarkable advances can be seen in the areas of imaging technologies and advancement of hybrid methods to understand the structure and function of proteins. 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.

• Structure Determination

• Technological Advances In Existing Methods

• New And Potentially Disruptive Technologies

• Advances In Drug Design

• Advances In Tool Development

• Advances In Imaging Technologies

Structural Virology

Viruses use a molecular mechanism to invade the host cells to establish an infection and to ensure that the progeny virus particles are released into the environment invading the host’s immune defenses. This mechanism is known as Structural Virology. Although viruses are simple as the individual with the self –replicating ability but as a group, they are exceptionally diverse in strategies and structures.

Biomolecules

Biomolecules are molecules that are involved in the maintenance and metabolic processes of living organisms. These non-living molecules are the actual foot-soldiers of the battle of sustenance of life. They range from small molecules such as primary and secondary metabolites and hormones to large macromolecules like proteins, nucleic acids, carbohydrates, lipids etc.Biomolecules are usually involved in the maintenance & metabolic processes of living organisms. These molecules are non-living molecules for the battle of sustenance of life. They have a wide range of small molecules like primary & secondary metabolites to Large macromolecules like proteins, lipids, etc.Biomolecules are formed by joining many small units together to form a long chain. This process is called synthesis. These molecules are involved in the maintenance and metabolic processes of living organisms.

Structural Biology and Single Molecules

Single Molecules methods represent a truly novel approach to biochemical/biological problems. All classical structural and biochemistry/biophysics methods describe the behavior of enormous ensembles of molecules, averaging the measured parameters over the entire molecular population. How anyone molecule may behave over time cannot be revealed by such studies; neither can the behavior of individual molecules having different conformations and properties.SM methods provide the only available way to study their functional differences, by recording the behavior of individual members of a certain population of molecules. In addition, SM approaches reveal fluctuations in the observable parameters of a single molecule over time, often with very high temporal resolution, usually on the order of milliseconds. 

Single Molecules methods represent a truly novel approach to biochemical/biological problems. All classical structural and biochemistry/biophysics methods describe the behavior of enormous ensembles of molecules, averaging the measured parameters over the entire molecular population. How anyone molecule may behave over time cannot be revealed by such studies; neither can the behavior of individual molecules having different conformations and properties.SM methods provide the only available way to study their functional differences, by recording the behavior of individual members of a certain population of molecules. In addition, SM approaches reveal fluctuations in the observable parameters of a single molecule over time, often with very high temporal resolution, usually on the order of milliseconds. 

Structural Molecular Biology

Molecular biology is a branch of biochemistry which concerns the molecular basis of biological activity between biomolecules in the various systems of a cell, including the interactions between DNA, RNA, and proteins and their biosynthesis, as well as the regulation of these interactions

• Molecular cloning

• Polymerase chain reaction

• Gel electrophoresis

• Macromolecule blotting and probing

• Microarrays

• Allele-specific oligonucleotide

Structural Bioinformatics and Proteomics

Structural biology determines the 3-D shape of a protein letting us know how a protein functions and the role it plays within a cell. Bioinformatics data is derived from structural determination experiments which provide biological researchers to ask a variety of questions and allowing them to understand how DNA mutations might alter a protein’s shape, disrupt a catalytic site, or alter the binding affinity of a pharmaceutical compound. Proteomics is the large-scale study of proteomes. A proteome is a set of proteins produced in an organism, system, or biological context. The proteome differs from cell to cell and changes over time. The protein activity is also modulated by many factors in addition to the expression level of the relevant gene. Several high-throughput technologies have been developed to investigate proteomes in depth like mass spectrometry-based techniques and gel-based techniques.