Drug discovery is the main problem of medicinal chemistry. It is important to make the process of finding new medications rational and worthwhile. This goal can be achieved by techniques of computational chemistry such as molecular modeling. The use of computer, molecular modeling in particular, for drug research is an actual issue of modern science. Improvement of computational chemistry techniques can lead to invention of universal medications or medicines with no side effects. Molecular modeling can even replace clinical laboratory tests. The aim of this article is to review basic molecular modeling methods and to give the examples of how these methods help in discovery of new drugs.
Molecular modeling is one of the main techniques of computational chemistry. It encompasses all theoretical methods and computational procedures used to model or simulate the behaviour of molecules. A fundamental constituent of molecular modeling is optimization. The determination of a low-energy conformation for a given force field can be the final goal of the computation. In molecular modeling a molecule can be represented in two ways. According to molecular mechanics, molecule is treated as a mechanical system where the particles (atoms) are connected by springs (bonds). The molecule rotates, vibrates, and translates to take on favored conformations in space as a reaction on different forces acting upon it. Quantum chemistry approach suggests that molecule is a system of electrons and nucleus that obeys the quantum mechanics laws.
The two major computational methods of molecular modeling are Monte Carlo method (MC) and molecular dynamics (MD). MC methods are based on repeated random sampling to obtain numerical results. MD is a way to computationally simulate the movement of particles and it is widely used to provide a dynamic perspective on biomolecules.
Drug discovery is a difficult expensive process of great importance. It includes four stages:
- target identiﬁcation and validation
- lead identiﬁcation
- lead optimization
- biological testing
The main problem of drug discovery is to predict if a given molecule will bind to a target. It is solved by application of such molecular modeling methods as generation of chemical structure, visualization of molecular structure, determination of molecular properties, molecular docking and others. The use of these techniques reduces prices of drug discovery process. Computational tools are less costly than any laboratory test.
Molecular modeling has already proved its high potency being employed for discovery of anticancer agents, synthetic analogues of natural compounds, etc. One of the most remarkable achievements of modern medicine was the discovery of drugs that attack HIV-1 protease – the main target of AIDS therapy. It became possible due to molecular modeling techniques.
Molecular modeling techniques applied in medications finding provide useful insights, new suggestions for molecular structures to synthesize, and cost-effective experimental analysis prior to synthesis. Thus, the use of molecular modeling methods for discovering and designing new drugs is a central topic in modern molecular biology and medicinal chemistry.
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