Structural bioinformatics is the branch of bioinformatics that is related to the analysis and prediction of the three-dimensional structure of biological macromolecules such as proteins, RNA, and DNA. It deals with generalizations about macromolecular 3D structures such as comparisons of overall folds and local motifs, principles of molecular folding, evolution, binding interactions, and structure/function relationships, working both from experimentally solved structures and from computational models. The term structural has the same meaning as in structural biology, and structural bioinformatics can be seen as a part of computational structural biology. The main objective of structural bioinformatics is the creation of new methods of analysing and manipulating biological macromolecular data in order to solve problems in biology and generate new knowledge.
Drug design, often referred to as rational drug design or simply rational design, is the inventive process of finding new medications based on the knowledge of a biological target. The drug is most commonly an organic small molecule that activates or inhibits the function of a biomolecule such as a protein, which in turn results in a therapeutic benefit to the patient. In the most basic sense, drug design involves the design of molecules that are complementary in shape and charge to the biomolecular target with which they interact and therefore will bind to it. Drug design frequently but not necessarily relies on computer modeling techniques. This type of modeling is sometimes referred to as computer-aided drug design. Finally, drug design that relies on the knowledge of the three-dimensional structure of the biomolecular target is known as structure-based drug design. In addition to small molecules, biopharmaceuticals including peptides and especially therapeutic antibodies are an increasingly important class of drugs and computational methods for improving the affinity, selectivity, and stability of these protein-based therapeutics have also been developed.
In the field of molecular modeling, docking is a method which predicts the preferred orientation of one molecule to a second when a ligand and a target are bound to each other to form a stable complex. Knowledge of the preferred orientation in turn may be used to predict the strength of association or binding affinity between two molecules using, for example, scoring functions.
Protein–ligand docking is a molecular modelling technique. The goal of protein–ligand docking is to predict the position and orientation of a ligand when it is bound to a protein receptor or enzyme. Pharmaceutical research employs docking techniques for a variety of purposes, most notably in the virtual screening of large databases of available chemicals in order to select likely drug candidates. There has been rapid development in computational ability to determine protein structure with programs such as AlphaFold, and the demand for the corresponding protein-ligand docking predictions is driving implementation of software that can find accurate models. Once the protein folding can be predicted accurately along with how the ligands of various structures will bind to the protein, the ability for drug development to progress at a much faster rate becomes possible.
Virtual screening (VS) is a computational technique used in drug discovery to search libraries of small molecules in order to identify those structures which are most likely to bind to a drug target, typically a protein receptor or enzyme.
In molecular modelling, docking is a method which predicts the preferred orientation of one molecule to another when bound together in a stable complex. In the case of protein docking, the search space consists of all possible orientations of the protein with respect to the ligand. Flexible docking in addition considers all possible conformations of the protein paired with all possible conformations of the ligand.
In the fields of computational chemistry and molecular modelling, scoring functions are mathematical functions used to approximately predict the binding affinity between two molecules after they have been docked. Most commonly one of the molecules is a small organic compound such as a drug and the second is the drug's biological target such as a protein receptor. Scoring functions have also been developed to predict the strength of intermolecular interactions between two proteins or between protein and DNA.
Chemical Computing Group is a software company specializing in research software for computational chemistry, bioinformatics, cheminformatics, docking, pharmacophore searching and molecular simulation. The company's main customer base consists of pharmaceutical and biotechnology companies, as well as academic research groups. It is a private company that was founded in 1994; it is based in Montreal, Quebec, Canada. Its main product, Molecular Operating Environment (MOE), is written in a self-contained programming system, the Scientific Vector Language (SVL).
Inte:Ligand was founded in Maria Enzersdorf, Lower Austria (Niederösterreich) in 2003. They established the company headquarters on Mariahilferstrasse in Vienna, Austria that same year.
MacroModel is a computer program for molecular modelling of organic compounds and biopolymers. It features various chemistry force fields, plus energy minimizing algorithms, to predict geometry and relative conformational energies of molecules. MacroModel is maintained by Schrödinger, LLC.
AutoDock is a molecular modeling simulation software. It is especially effective for protein-ligand docking. AutoDock 4 is available under the GNU General Public License. AutoDock is one of the most cited docking software applications in the research community. It is used by the FightAIDS@Home and OpenPandemics - COVID-19 projects run at World Community Grid, to search for antivirals against HIV/AIDS and COVID-19. In February 2007, a search of the ISI Citation Index showed more than 1,100 publications had been cited using the primary AutoDock method papers. As of 2009, this number surpassed 1,200.
The program UCSF DOCK was created in the 1980s by Irwin "Tack" Kuntz's Group, and was the first docking program. DOCK uses geometric algorithms to predict the binding modes of small molecules. Brian K. Shoichet, David A. Case, and Robert C.Rizzo are codevelopers of DOCK.
Lead Finder is a computational chemistry tool designed for modeling protein-ligand interactions. This application is useful for conducting molecular docking studies and quantitatively assessing ligand binding and biological activity. Lead Finder offers free access to individual users, especially those in non-commercial and academic settings.
Discovery Studio is a suite of software for simulating small molecule and macromolecule systems. It is developed and distributed by Dassault Systemes BIOVIA.
Scigress, stylized SCiGRESS, is a software suite for molecular modelling, computational chemistry, drug design, and materials science, a successor to Computer Aided Chemistry (CAChe) software.
DelPhi is a scientific application which calculates electrostatic potentials in and around macromolecules and the corresponding electrostatic energies. It incorporates the effects of ionic strength mediated screening by evaluating the Poisson-Boltzmann equation at a finite number of points within a three-dimensional grid box. DelPhi is commonly used in protein science to visualize variations in electrostatics along a protein or other macromolecular surface and to calculate the electrostatic components of various energies.
LiSiCA is a ligand-based virtual screening software that searches for 2D and 3D similarities between a reference compound and a database of target compounds which should be represented in a Mol2 format. The similarities are expressed using the Tanimoto coefficients and the target compounds are ranked accordingly. LiSiCA is also available as LiSiCA PyMOL plugin both on Linux and Windows operating systems.
Molecular Operating Environment (MOE) is a drug discovery software platform that integrates visualization, modeling and simulations, as well as methodology development, in one package. MOE scientific applications are used by biologists, medicinal chemists and computational chemists in pharmaceutical, biotechnology and academic research. MOE runs on Windows, Linux, Unix, and macOS. Main application areas in MOE include structure-based design, fragment-based design, ligand-based design, pharmacophore discovery, medicinal chemistry applications, biologics applications, structural biology and bioinformatics, protein and antibody modeling, molecular modeling and simulations, virtual screening, cheminformatics & QSAR. The Scientific Vector Language (SVL) is the built-in command, scripting and application development language of MOE.
FlexAID is a molecular docking software that can use small molecules and peptides as ligands and proteins and nucleic acids as docking targets. As the name suggests, FlexAID supports full ligand flexibility as well side-chain flexibility of the target. It does using a soft scoring function based on the complementarity of the two surfaces.
rDock is an open-source molecular docking software that be used for docking small molecules against proteins and nucleic acids. It is primarily designed for high-throughput virtual screening and prediction of binding mode.
