Computational toxicology: fast, economical and ethical

ProtoQSAR is a company that conducts studies for its clients and collaborators, currently we do not sell molecular simulation programs, nor our QSAR models. We provide our services to groups and entities that for the most part do not have specific training in chemistry-computing and molecular modeling -or it is very limited- and therefore our expertise can represent a greater added value for them.

The projects in which we work are very different from each other, and prior to their execution we make an evaluation of the time necessary. The great advantage of computer studies compared to experimental tests is that we can obtain results in a much shorter time. For example, the prediction of the profile of a compound by QSAR methods is very fast (few days), since we already have models for this kind of evaluation. The virtual screening of a database to search for a candidate interacting with a particular target can represent 1 week to 2 months, depending on the number of chemicals filtered (a few thousands or hundreds of thousands).

At ProtoQSAR we are very interested in the development of new collaborative projects in which chemoinformatics and molecular modeling can provide an added value to our collaborators. If you have any idea to raise, please contact us explaining your proposal, and in a very short time we will give you an answer.

Costs vary depending on the type of service we provide and the time we spend on a project. Since computing allows results to be obtained in a much shorter time than experimental tests, our services are also much cheaper.

In ProtoQSAR we work with the whole palette of molecular modeling and chemoinformatics techniques, and therefore we have all the necessary programs for the execution of our projects. We systematically use standardized programs that are well referenced in the scientific literature, and sometimes we carry out our own software developments for specific needs. In any case, these developments remain the property of ProtoQSAR, and are not for sale.

Computational studies are not an “exact science” and a certain degree of uncertainty is expected, as is the case with experimental tests (both in vitro and in vivo) to a certain extent. We conduct our studies according to scientifically recognized quality guidelines, and our extensive experience (demonstrable through our scientific and technical publications) makes our studies as accurate as possible. Before conducting a study, we inform our clients about the reasonable results’ expectations. At the time of providing the results, we also contribute our expert evaluation and inform the customer of the potential limitations of the obtained models.

Both questions are linked: the execution time of a virtual screening depends essentially on the number of compounds that are screened. To give a general idea, an already developed QSAR model allows the user to evaluate tens of thousands of compounds in a single day. Screening by docking (in a therapeutic target with known 3D structure) requires a longer period of time, but we can also evaluate thousands of compounds in a few days.

Chemoinformatic models are recognized as a valid alternative at a the regulatory level, and the international regulations themselves increasingly encourage their use. For example, in the case of REACH, ECHA systematically requests companies to demonstrate that they have fully considered the use of alternative methods before concluding that a new test with vertebrates is necessary.

Yes, in a lot of cases our models make it unnecessary to perform additional assays. This is particularly common when there is already some bibliographic information on the studied compounds, or when the products are of natural origin. In other cases the computational studies do not completely replace the experimental tests, but it is usually possible to reduce them (and therefore reduce time and costs). Another factor to consider is the credibility of the company in front of the authorities, which is clearly favored when presenting a complete dossier including the evaluation by alternative methods.

The type of model depends on the baseline information and on the substance to be evaluated. In principle, QSAR models are technically more robust and reliable, but they cannot always be used (for example, if the compound to be evaluated does not fall within the domain of applicability of the compounds that have been used to generate the models). In that case read-across is a good alternative, since this technique has the same validity at the regulatory level when properly executed by an experienced professional.

Applicability domain is the “chemical space” to which a specific compound belongs in relation to the compounds that have served as the basis for developing a QSAR model. One of the parameters required by the OECD (and therefore necessary from a regulatory point of view) when determining whether a QSAR is valid on a given compound is the characterization of that space.

All our models are subjected to a double validation, internal and external, and when possible we perform an experimental validation with independent structures belonging to the same chemical space or “domain of applicability”.