‘In Silico’ Research and Virtual Screening in Drug Discovery

In the second week of March 2014, a new class of antibiotics to fight bacteria such as methicillin-resistant Staphylococcus aureus and other drug-resistant bacteria that threaten public health has been discovered by a team of chemists. The new class, called oxadiazoles, was discovered in silico screening and has shown promise in the treatment of MRSA in mouse models of infection. We note here that MRSA has become a global public-health problem since the 1960s because of its resistance to antibiotics. This article discusses various developments in in silico screening / Virtual screening.

Latin Phrases

Various Latin expressions are used to describe the research carried out in various ways.

For example, in situ means that the research was carried out exactly in place where it occurs, i.e. without moving it to some special medium. In biology, particularly, the cell science, the three phrases, in vivo, in situ and in vitro represent three consecutive stages of an experiment or observation.

In vivo means ‘within the living’. In vivo means that research was done using a whole, living organism as opposed to a partial or dead organism. Two common forms of in vivo research include animal studies and clinical trials. The objective of in vivo research is to observe overall effects of an experiment.

In case of lab science, the term “in situ” comes somewhere between the in vivo and in vitro. For instance, examining a cell within a whole organ of a live lab mouse if in vivo experiment, but taking out that organ and then performing an examination is an in situ investigation. However, in –vitro is different. In vitro means in glass i.e. test tube. In vitro is used to express all experiments done in lab.

In vitro experiments essentially represent a controlled environment outside of a living organism. Many experiments in cellular biology are conducted outside of organisms or cells. The major problem with the in vitro experiments is that they fail to replicate the natural conditions of an organism, particularly a microbe.

In silico Research

If the research was carried out only on paper and no practical experiments done, it is “in papyro“, only in papers. In silico is also equivalent to in papyro; only difference is that it is performed on computer or via computer simulation. This term has become of high importance in Drug discovery in recent times. With reference to lab science, in silico are the biological experiments essentially carried out entirely in a computer.

There are many in silico techniques. Three most important are Bacterial sequence techniques, Molecular modelling and whole cell simulations.

Virtual Screening

In recent times, Virtual screening has emerged as an important tool in identifying bioactive compounds through computational means, by employing knowledge about the protein target or known bioactive ligands. It basically helps to screen against any given target and/or property millions or perhaps billions of molecules in short period of time and access novel drug like compounds and in drug discovery. One example is a 2008 research on African sleeping sickness disease. We note here that only one new drug to treat African sleeping sickness has appeared in the past 50 years.

A team led by University of California computational biologist used Virtual Screening approach to identify five compounds that could lead to new drugs to combat the disease. The compounds block the activity of the trypanosomal REL1 enzyme, which the parasite needs to survive. To arrive at those compounds, the researchers searched a large database of existing compounds for structurally similar molecules. When they tested their best candidates experimentally, five inhibited REL1. These five molecules, which block the activity of a crucial trypanosomal enzyme, could now serve as the basis for future drug design and discovery efforts. The same team had also used it to develop a model for a new class of drugs to treat AIDS that led to raltegravir, which the Food and Drug Administration approved in 2007.