Chemical Biology & Drug Design

The use of molecular dynamics in drug design is demonstrated, using compstatin family peptides as a paradigm. Analogs with novel properties are presented using the following design criteria: (i) optimization for high binding affinity and for the balance between hydrophobicity and polarity to improve solubility, compared to known compstatin analogs; and (ii) development of dual specificity antihuman-rat/mouse C3 analogs, which is important for use in animal models for disease, given the species specificity of known compstatin analogs.

Linear and non-linear QSAR models were developed and validated using FS-MLR, ERM-MLR and SVMR methods for isoindolinone-based p53-MDM2 interaction inhibitors.