The alert “Substituted phenols” in MNT model is identical to the alert “Substituted phenol” part of endpoint specific “Protein binding alerts for CA by OASIS v1.2 profiler”. The same alert implemented in the general mechanistic “Protein binding alert by OASIS v1.4” is more generalized (not so restrictive) than the endpoint specific one given the fact that it provides only indication for interaction with proteins. In this respect alert part of general Protein binding profiler is not identical to the endpoint specific “Substituted phenol” alert from TIMES MNT model. The latter is due to the assumption that not all protein binding interactions are producing chromosomal aberrations associated with micronucleus effects.

We keep full consistency between alerts (DNA and Protein) in QSAR Toolbox and TIMES. What mean this consistency?

There are two types of Protein and DNA binding profilers placed in two sections: general and endpoint specific. The consistency mentioned above holds for alerts in Endpoint specific profilers. In other words there is a full consistency between endpoint-specific “Protein binding alerts for CA v1.2” and protein binding alerts implemented in TIMES MNT and CA models. Similarly, this holds for DNA binding profilers and alerts.

In the General mechanistic Protein (DNA) binding profilers, alerts are defined by more generalized structural boundaries (no restrictions here), which means that this alerts in these profilers could damage macromolecules. However, not always the damage causes endpoint effect. For example in General mechanistic Protein binding by OASIS v1.4 all peroxides are included: such as organic peroxides and hydroperoxides under Radical domain. However, only hydroperoxides could cause damage leading to SS. As a result if you view the alerts for Radical mechanism in General mechanistic profiler you will see two alerts included (see Figure 1):

  • Organic peroxy compound
  • Hydroperoxide

On the other hand protein binding alerts for Skin sensitization by OASIS v1.4 include only one alert - Hydroperoxide (Figure 1):

  • Hydroperoxide

Figure 1 Excerpt of general and endpoint specific protein binding profilers

Same is the situation with DNA alerts. For example in Figure 2 is illustrated how Endpoint specific DNA alerts for Ames by OASIS v1.4 are more specific (with more restrictions) than in General mechanistic DNA binding by OASIS v1.1. This is illustrated for one alert “Single ring substituted primary aromatic amine”. According to General mechanistic profile this alert is positive, while according to Endpoint specific profile it is negative.

Figure 2 Discrepancy of boundaries across General and Endpoint specific DNA alerts