The PeptiMOL project has been executed via six work packages as planned:
- WP1: the relevant peptides to develop the chemoinformatic models were selected. First the available QSPKR models on therapeutic peptides were compiled and analyzed, and secondly the information was filtered and curated by means of advanced data mining techniques in order to define the families of peptides for our study.
- WP2: molecular descriptors specifically tailored for peptides were designed and calculated for the datasets coming from WP1. To do this, a user-friendly software called PeptiDesCalculator was developed in Java language.
- WP3: QSPKR models were developed by applying a variety of statistical and machine learning techniques. Those models were possible thanks to a previous selection of the most adapted descriptors, and a random split of the datasets into training and validation groups. Each model was assessed for its robustness and predictivity by the calculation of the standard statistical parameters, such as accuracy, sensitivity and specificity. Furthermore, the applicability domain of the models was alto established, to elucidate the chemical space for which the models’ predictions are reliable. Finally, as a proof of concept, an experimental validation of one of the models (solubility) was done on a set of 50 peptides thanks to a secondment in the Centro de Investigación Príncipe Felipe (CIPF) de Valencia, as planned in the proposal.
- WP4: the QSPKR models were implemented in a innovative platform, PeptiKinetics, in order to facilitate the use of any person interested in those models, independently of their level of experience on this field.
- WP5: management and monitoring.
- WP6: dissemination within the industrial community and general public, IPR management.
At the end of the project, the main results achieved were the two pieces of software:
a) PeptiDesCalculator software, a standalone software that computes theoretical descriptors for peptide molecules represented as strings of standard amino acid sequences. PeptiDesCalculator computes a total of 48485 molecular descriptors. PeptiDesCalculator is developed in Java programming language (version 9.0.4) and it was designed to run on any UNIX/LINUX or MAC platforms, as well as on microcomputers running Windows 95, 98, ME, 2000 or XP, Vista, 7 and above. It requires Java(TM) 7 Runtime Environment on the target system and also works on X86 and X64 based architecture.
b) PeptiKinetics software, a standalone software that computes the pharmacokinetic properties of peptide molecules to allow for the design of new peptide chains adapted to the therapeutic profile of interest, and with adequate bioavailability. These properties are implemented as mathematical models developed using an array of statistical and machine learning techniques and peptide descriptors computed with the inhouse PeptiDesCalculator repository. The implemented pharmacokinetics properties include: plasma half-life, Caco-2 permeability (Paap), blood brain barrier passage, aqueous solubility, cell penetrating peptide (CPP) uptake and haemolytic activity.
- Programming Language: PeptiKinetics is developed in Java programming language (version 9.0.4) and can thus be run on any operating system that has the Java Virtual Machine (JVM) installed. PeptiKinetics was designed to run on any UNIX/LINUX or MAC platforms, as well as on microcomputers running Windows 95, 98, ME, 2000 or XP, Vista, 7 and above.
