People often ask about what our company, SARomics Biostructures, does. For us who work within the field, it is sometimes easy to forget that other people may not know so much about the details of what we do. We need to explain this more often and this text is an attempt to do just that, to start a project to give our followers and all those interested in the subject an idea about the general principles of structure-based drug design. In future posts I plan to describe in more detail and compare the experimental methods we apply in our work.

Let us first start with “when”. When do we need structural biology in drug discovery and design? To answer this, I have added a summary scheme of the drug discovery process. To demonstrate the highly interdisciplinary character of the process, the different scientific disciplines required at different stages are also shown. An approximate time scale illustrating the duration of the different stages is also given.

This scheme answers the above “when”-question. Structural biology is mostly required at the early stages of the process, that is, hit identification, lead generation and lead optimization. A “hit” is a molecule with some degree of activity towards the target, identified during an initial small molecule compound library screening (hit identification). This molecule normally needs to be modified in multiple cycles (lead generation) to reach a compound with better activity parameters (a lead). This is the stage at which structural biology and bioinformatics are most useful. The next stage, which is lead optimization, involves the improvement of the pharmacokinetic properties of the ligand by optimization of such parameters as absorption, distribution, metabolism, excretion, toxicity, etc. Of course, even here structural biology can be of great help.

In a small review paper published in 2006 Tom Blundell, one of the pioneers of the application of X-ray crystallography to drug discovery, wrote that in the early days of X-ray crystallography pharmaceutical companies did not want to put money into structural methods because they thought that it was “too expensive and time consuming to bring in house”. However, nowadays essentially all large pharma companies have in-house structural groups, and several service companies (contact research organizations, CRO), like SARomics Biostructures, have emerged.

Time is money, and structural biology tools have become essential in the acceleration of the drug discovery process. The ability of the structure to reveal details of the interactions of ligands with the binding site of the target provides direct insights that help improv the design of compounds. This is what we do at SARomics Biostructures.

In the following posts I will go into details of the methods and give some illustrations. At some moment I will disclose what SAR in SARomics actually means. 

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Blundell et all. (2006). Phil. Trans. R. Soc. B 361, 413–423